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Adipose Tissue‐Derived Plasminogen Activator Inhibitor‐1 Function and Regulation

Hiroshi Kaji

10.1002/cphy.c160004

Source: Volume 6, Issue 4, October 2016

Published online: September 2016

Full Article on Wiley Online Library



ABSTRACT

Adipose tissue has recently been reevaluated as an endocrine organ, and adipose‐tissue‐derived endocrine factors are termed adipokines. Plasminogen activator inhibitor‐1 (PAI‐1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI‐1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI‐1 exerts various cellular effects independently of fibrinolysis. Although PAI‐1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner. Adipocyte‐derived PAI‐1, predominantly expressed in visceral fat, is released into the circulation in parallel with increased fat mass, and it functions as a crucial adipokine that negatively affects physiological metabolism and vascular biology. Elevated PAI‐1 levels induce insulin resistance and metabolic abnormalities during proinflammatory processes involving several cytokines and chemokines in diabetes. Several studies have indicated that PAI‐1 plays crucial roles in insulin actions on liver, muscle, and fat. Accumulated fat and enhanced adipose tissue‐derived PAI‐1 influence metabolism and vessels in relation to macrophage infiltration, chronic inflammation, and free fatty acid release in obese states. PAI‐1‐induced fibrinolysis abnormalities are associated with metabolic syndrome, leading to cardiovascular disease through dysregulated vascular coagulation, endothelial dysfunction, and metabolic abnormalities. Adipose tissue‐derived PAI‐1 is involved in insulin resistance, osteoporosis, and sarcopenia induced by glucocorticoid excess in mice. Moreover, PAI‐1 is involved in the other pathological states, such as nonalcoholic fatty liver disease, and cancer. As such, PAI‐1 may be exploited as a marker of disease activity as well being a target for clinical drug development. © 2016 American Physiological Society. Compr Physiol 6:1873‐1896, 2016.

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Figure 1. Figure 1. Fibrinolytic system. Plasminogen is converted into plasmin by tPA and uPA. Plasmin resolves the formed fibrin clots by fibrinolysis. PAI‐1 is the most important inhibitor of tPA and uPA. PAI‐1 activation suppresses fibrinolysis, resulting in enhanced fibrinogenesis. FDP, fibrin degradation products.
Figure 2. Figure 2. Fibrinolysis‐independent effects of PAI‐1PAI‐1 interacts with cell surface receptors, vitronectin, uPA/uPAR complexes, and LRP 1. Cells localize both uPA and PAI‐1 leading to the modulation of interrelated events involving extracellular matrix proteins and cell functions, such as migration, proliferation, differentiation, and apoptosis. In this reaction, uPA interacts with cell surface uPAR, and PAI‐1 binds to uPA/uPAR or vitronectin. Subsequent tissue proteolysis modulates extracellular matrix architecture and influences cell‐matrix interactions through integrin receptors and the release of bioactive factors and growth factors affecting cellular functions. LRP1 ligand binding and its complex formation with integrins, growth factor receptors, and proteoglycans induces various protein kinases. Data, with permission, from Czekay et al., Ref. 32.
Figure 3. Figure 3. Human PAI‐1 promoter and transcription factor binding sites. AP‐1, Activator protein 1‐like binding element; E, E‐box; FKHR, FoxO/forkhead like binding element; HRE, hypoxia response element; NBRE, NGF1‐β responsive element/Nurr77 response element; SP1, stimulatory protein‐1 response element; SRE, Smad3/4‐binding element/TGF‐β response element; VLDL‐RE, very‐low‐density lipoprotein response element. Data, with permission, from Dimova et al., Ref. 39.
Figure 4. Figure 4. Role of adipose tissue‐derived PAI‐1 in various diseases. Adipose tissue includes adipocytes, macrophages, and vessels. These cells participate in the production of adipokines. The accumulation of fat in adipose tissue and adipokines secreted from adipose tissue are associated with various diseases. PAI‐1 is a crucial adipokine that negatively affects physiological cellular events through mechanisms dependent on and independent of fibrinolysis. The elevations in PAI‐1, TNF‐α, IL‐1, IL‐6, MCP‐1, leptin, and free fatty acids released from adipose tissue as well as a decrease in adiponectin are related to insulin resistance, cardiovascular disease, osteoporosis, sarcopenia, senescence, and cancer. Obesity, inflammation, hypoxia, stress, and corticosteroids induce the dysregulation of adipokine secretion from adipose tissue as well as adipocyte hypertrophy. MCP‐1, monocyte chemoattractant protein‐1.
Figure 5. Figure 5. Role of adipose‐derived MCP‐1 in stress response to diabetes. The diabetes‐induced stress response is composed of two pathways via the sympathetic nervous system leading to the secretion of catecholamines and the hypothalamic‐pituitary‐adrenal axis leading to an increase in glucocorticoids. Macrophage accumulation in adipose tissue is related to the secretion of inflammatory adipokines and the release of free fatty acids related to lipolysis. This pathological modulation promotes the imbalance of glucose metabolism and the coagulation system. Acute stress induces a thrombotic tendency with increases in PAI‐1 levels derived from adipose tissues. Stress induces the production of MCP‐1 from adipose stromal cells, then enhances adipose inflammation and the secretion of proinflammatory adipokines, such as PAI‐1. These adipokines lead to procoagulatory state and insulin resistance, TNF‐α and IL‐6 enhance the production of MCP‐1 from adipocytes and endothelial cells in adipose tissue, and monocytes infiltrating into adipose tissue in response to MCP‐1 secrete TNF‐α and IL‐6. Thus, adipose tissue‐derived MCP‐1 enhances the amplification cascade during chronic inflammation in adipose tissue through autocrine and paracrine interactions among macrophages, adipocytes, and endothelial cells under stress conditions and in the diabetic state. Data, with permission, from Uchida et al., Ref. 181.
Figure 6. Figure 6. Role of PAI‐1 in diabetic osteoporosis in female mice. The diabetic state enhances the expression of PAI‐1 in the liver, leading to an elevation in circulating PAI‐1 levels in female mice. Then, circulating PAI‐1 suppresses osteoblast differentiation and mineralization, although it enhances adipogenesis in bone marrow tissue, resulting in diabetic osteoporosis. Data, with permission, from Tamura et al., Ref. 172.
Figure 7. Figure 7. Diabetes, PAI‐1, and adipose‐derived stem cells. Adipose‐derived stem cells are clinically useful for tissue repair and regeneration. Angiogenesis is important for the induction of tissue repair by adipose‐derived stem cells. PAI‐1 levels from adipose‐derived stromal cells are elevated in patients with diabetes, leading to a decrease in angiogenic activity by adipose‐derived stromal cells. Adipose tissue‐derived PAI‐1 might limit the angiogenic activity during tissue repair and regeneration by adipose‐derived stem cells in diabetes. PAI‐1 affects uPA that induces the production of plasmin by the cleavage of plasminogen and the activation of MMPs and growth factors in tissue as well as an activation of urokinase plasminogen activator receptor (uPAR) on the cell surface. This uPA system is important for the migration and invasion of vascular endothelial cells as well as the maintenance of an adequate cell microenvironment during tissue repair. An elevation in circulating and tissue PAI‐1 expression in diabetes may contribute to a decrease in fibrinolytic activity of adipose‐derived stem cells as well as in the cell microenvironment during tissue repair. Data, with permission, from Acosta et al., Ref. 3; Dzhoyashvili et al., Ref. 41; and Tashiro et al., Ref. 176. VEGF, vascular endothelial growth factor.
Figure 8. Figure 8. The mechanism by which obesity induces proinflammatory adipokines. Obesity induced by excessive food intake is characterized by the chronic and excessive accumulation of fat and subsequent metabolic disorders with low‐intensity chronic inflammation, resulting in insulin resistance, cardiovascular disease, and hyperlipidemia. Adipocyte hypertrophy, accelerated adipocyte differentiation, macrophage infiltration, insulin resistance, and the release of inflammatory adipokines and free fatty acids are induced by obesity in adipose tissue. The production of PAI‐1 by adipose tissue is enhanced in obesity because of an increase in fat mass and activation of the proinflammatory state of adipokines in the microenvironment of adipose tissue. Elevated circulating PAI levels are due to an enhancement of PAI‐1 production from adipocytes, macrophages, and vascular endothelial cells in adipose tissue as well as the release of PAI‐1 from the liver.
Figure 9. Figure 9. Role of PAI‐1 and TNF‐α in obesity‐induced glucose/lipid metabolism abnormalities and osteopenia. PAI‐1 deficiency improved insulin resistance and high serum cholesterol levels induced by obesity in female mice, although it did not affect trabecular bone loss and impaired osteoblast differentiation induced by obesity. Obesity induces insulin resistance and hyperlipidemia through PAI‐1, although obesity‐related trabecular bone loss was independent of PAI‐1. On the other hand, TNF‐α seemed to be related to obesity‐induced osteopenia in mice independently of PAI‐1. Data, with permission, from Tamura et al., Ref. 173.
Figure 10. Figure 10. Role of PAI‐1 in glucocorticoid‐induced diabetes, osteoporosis, and muscle wasting. Glucocorticoid enhances PAI‐1 expression in adipose tissue, contributing to an increase in circulating PAI‐1 levels. This elevation in circulating PAI‐1 induces insulin resistance in the liver, osteoporosis, and muscle wasting in mice. Adipose tissue‐derived PAI‐1 may be important in the pathogenesis of the major adverse effects of glucocorticoid treatment. Data, with permission, from Tamura et al., Ref. 174.
Figure 11. Figure 11. Mechanism of PAI‐1 actions on bone. PAI‐1 suppresses the levels of osteoblast differentiation markers such as Runx2, Osterix, and alkaline phosphatase in female, but not male murine osteoblasts. Moreover, PAI‐1 deficiency blunts osteoblast differentiation suppressed by diabetes and adipogenic differentiation promoted by diabetes in bone tissue from female, but not male mice. On the other hand, PAI‐1 induced the apoptosis of osteoblasts, although it did not affect the proliferation of osteoblasts in both male and female mice. Data, with permission, from Tamura et al., Ref 172,174.


Figure 1. Fibrinolytic system. Plasminogen is converted into plasmin by tPA and uPA. Plasmin resolves the formed fibrin clots by fibrinolysis. PAI‐1 is the most important inhibitor of tPA and uPA. PAI‐1 activation suppresses fibrinolysis, resulting in enhanced fibrinogenesis. FDP, fibrin degradation products.


Figure 2. Fibrinolysis‐independent effects of PAI‐1PAI‐1 interacts with cell surface receptors, vitronectin, uPA/uPAR complexes, and LRP 1. Cells localize both uPA and PAI‐1 leading to the modulation of interrelated events involving extracellular matrix proteins and cell functions, such as migration, proliferation, differentiation, and apoptosis. In this reaction, uPA interacts with cell surface uPAR, and PAI‐1 binds to uPA/uPAR or vitronectin. Subsequent tissue proteolysis modulates extracellular matrix architecture and influences cell‐matrix interactions through integrin receptors and the release of bioactive factors and growth factors affecting cellular functions. LRP1 ligand binding and its complex formation with integrins, growth factor receptors, and proteoglycans induces various protein kinases. Data, with permission, from Czekay et al., Ref. 32.


Figure 3. Human PAI‐1 promoter and transcription factor binding sites. AP‐1, Activator protein 1‐like binding element; E, E‐box; FKHR, FoxO/forkhead like binding element; HRE, hypoxia response element; NBRE, NGF1‐β responsive element/Nurr77 response element; SP1, stimulatory protein‐1 response element; SRE, Smad3/4‐binding element/TGF‐β response element; VLDL‐RE, very‐low‐density lipoprotein response element. Data, with permission, from Dimova et al., Ref. 39.


Figure 4. Role of adipose tissue‐derived PAI‐1 in various diseases. Adipose tissue includes adipocytes, macrophages, and vessels. These cells participate in the production of adipokines. The accumulation of fat in adipose tissue and adipokines secreted from adipose tissue are associated with various diseases. PAI‐1 is a crucial adipokine that negatively affects physiological cellular events through mechanisms dependent on and independent of fibrinolysis. The elevations in PAI‐1, TNF‐α, IL‐1, IL‐6, MCP‐1, leptin, and free fatty acids released from adipose tissue as well as a decrease in adiponectin are related to insulin resistance, cardiovascular disease, osteoporosis, sarcopenia, senescence, and cancer. Obesity, inflammation, hypoxia, stress, and corticosteroids induce the dysregulation of adipokine secretion from adipose tissue as well as adipocyte hypertrophy. MCP‐1, monocyte chemoattractant protein‐1.


Figure 5. Role of adipose‐derived MCP‐1 in stress response to diabetes. The diabetes‐induced stress response is composed of two pathways via the sympathetic nervous system leading to the secretion of catecholamines and the hypothalamic‐pituitary‐adrenal axis leading to an increase in glucocorticoids. Macrophage accumulation in adipose tissue is related to the secretion of inflammatory adipokines and the release of free fatty acids related to lipolysis. This pathological modulation promotes the imbalance of glucose metabolism and the coagulation system. Acute stress induces a thrombotic tendency with increases in PAI‐1 levels derived from adipose tissues. Stress induces the production of MCP‐1 from adipose stromal cells, then enhances adipose inflammation and the secretion of proinflammatory adipokines, such as PAI‐1. These adipokines lead to procoagulatory state and insulin resistance, TNF‐α and IL‐6 enhance the production of MCP‐1 from adipocytes and endothelial cells in adipose tissue, and monocytes infiltrating into adipose tissue in response to MCP‐1 secrete TNF‐α and IL‐6. Thus, adipose tissue‐derived MCP‐1 enhances the amplification cascade during chronic inflammation in adipose tissue through autocrine and paracrine interactions among macrophages, adipocytes, and endothelial cells under stress conditions and in the diabetic state. Data, with permission, from Uchida et al., Ref. 181.


Figure 6. Role of PAI‐1 in diabetic osteoporosis in female mice. The diabetic state enhances the expression of PAI‐1 in the liver, leading to an elevation in circulating PAI‐1 levels in female mice. Then, circulating PAI‐1 suppresses osteoblast differentiation and mineralization, although it enhances adipogenesis in bone marrow tissue, resulting in diabetic osteoporosis. Data, with permission, from Tamura et al., Ref. 172.


Figure 7. Diabetes, PAI‐1, and adipose‐derived stem cells. Adipose‐derived stem cells are clinically useful for tissue repair and regeneration. Angiogenesis is important for the induction of tissue repair by adipose‐derived stem cells. PAI‐1 levels from adipose‐derived stromal cells are elevated in patients with diabetes, leading to a decrease in angiogenic activity by adipose‐derived stromal cells. Adipose tissue‐derived PAI‐1 might limit the angiogenic activity during tissue repair and regeneration by adipose‐derived stem cells in diabetes. PAI‐1 affects uPA that induces the production of plasmin by the cleavage of plasminogen and the activation of MMPs and growth factors in tissue as well as an activation of urokinase plasminogen activator receptor (uPAR) on the cell surface. This uPA system is important for the migration and invasion of vascular endothelial cells as well as the maintenance of an adequate cell microenvironment during tissue repair. An elevation in circulating and tissue PAI‐1 expression in diabetes may contribute to a decrease in fibrinolytic activity of adipose‐derived stem cells as well as in the cell microenvironment during tissue repair. Data, with permission, from Acosta et al., Ref. 3; Dzhoyashvili et al., Ref. 41; and Tashiro et al., Ref. 176. VEGF, vascular endothelial growth factor.


Figure 8. The mechanism by which obesity induces proinflammatory adipokines. Obesity induced by excessive food intake is characterized by the chronic and excessive accumulation of fat and subsequent metabolic disorders with low‐intensity chronic inflammation, resulting in insulin resistance, cardiovascular disease, and hyperlipidemia. Adipocyte hypertrophy, accelerated adipocyte differentiation, macrophage infiltration, insulin resistance, and the release of inflammatory adipokines and free fatty acids are induced by obesity in adipose tissue. The production of PAI‐1 by adipose tissue is enhanced in obesity because of an increase in fat mass and activation of the proinflammatory state of adipokines in the microenvironment of adipose tissue. Elevated circulating PAI levels are due to an enhancement of PAI‐1 production from adipocytes, macrophages, and vascular endothelial cells in adipose tissue as well as the release of PAI‐1 from the liver.


Figure 9. Role of PAI‐1 and TNF‐α in obesity‐induced glucose/lipid metabolism abnormalities and osteopenia. PAI‐1 deficiency improved insulin resistance and high serum cholesterol levels induced by obesity in female mice, although it did not affect trabecular bone loss and impaired osteoblast differentiation induced by obesity. Obesity induces insulin resistance and hyperlipidemia through PAI‐1, although obesity‐related trabecular bone loss was independent of PAI‐1. On the other hand, TNF‐α seemed to be related to obesity‐induced osteopenia in mice independently of PAI‐1. Data, with permission, from Tamura et al., Ref. 173.


Figure 10. Role of PAI‐1 in glucocorticoid‐induced diabetes, osteoporosis, and muscle wasting. Glucocorticoid enhances PAI‐1 expression in adipose tissue, contributing to an increase in circulating PAI‐1 levels. This elevation in circulating PAI‐1 induces insulin resistance in the liver, osteoporosis, and muscle wasting in mice. Adipose tissue‐derived PAI‐1 may be important in the pathogenesis of the major adverse effects of glucocorticoid treatment. Data, with permission, from Tamura et al., Ref. 174.


Figure 11. Mechanism of PAI‐1 actions on bone. PAI‐1 suppresses the levels of osteoblast differentiation markers such as Runx2, Osterix, and alkaline phosphatase in female, but not male murine osteoblasts. Moreover, PAI‐1 deficiency blunts osteoblast differentiation suppressed by diabetes and adipogenic differentiation promoted by diabetes in bone tissue from female, but not male mice. On the other hand, PAI‐1 induced the apoptosis of osteoblasts, although it did not affect the proliferation of osteoblasts in both male and female mice. Data, with permission, from Tamura et al., Ref 172,174.
References
 1.Abranches MV, de Oliveira FCE, de Conceicao LL, de Carmo Gouveia Peluzio M. Obesity and diabetes: The link between adipose tissue dysfunction and glucose homeostasis. Nutr Res Rev 28: 121‐132, 2015.
 2.Abu‐Farha M, Behbehani K, Elkum N. Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs. Cardiovasc Diabetol 13: 76, 2014.
 3.Acosta L, Jmadcha A, Escacena N. Adipose mesenchymal stromal cells isolated from type 2 diabetic patients display reduced fibrinolytic activity. Diabetes 62: 4266‐4269, 2013.
 4.Agirbasli M, Eren M, Eren F, Murphy SB, Serdar ZA, Seckin D, Zara T, Cem Mat M, Demirkesen C, Vaughan DE. Enhanced functional stability of plasminogen activator inhibitor‐1 in patients with livedoid vasculopathy. J Thromb Thrombolysis 32:59‐63, 2011.
 5.Ahiwar AK, Jain A, Goswaml B, Bhatnagar MK, Bhatacharjee J. Imbalance between protective (adiponectin) and prothrombotic (plasminogen activator inhibitor‐1) adipokines in metabolic syndrome. Diabetes Metab Synd 8: 152‐155, 2014.
 6.Alessi MC, Bastelica D, Morange P, Berthet B, Ledue I, Verdier M, Geel O, Juhan‐Vague I. Plasminogen activator inhibitor 1, transforming growth factor‐β1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 49: 1374‐1380, 2000.
 7.Alessi MC, Juhan‐Vague I. PAI‐1 and the metabolic syndrome: Links, causes, and consequences. Arterioscler Thromb Vasc Biol 13: 162‐169, 1993.
 8.Alzamendi A, Castrogiovanni D, Ortega HH, Gaillard RC, Giovambattista A, Spinedi E. Parametrial adipose tissue and metabolic dysfunctions induced by fructose‐rich diet in normal and neonatal‐androgenized adult female rats. Obesity 18: 441‐448, 2010.
 9.Arenillas JF, Alvarez‐Sabín J, Molina CA, Chacón P, Fernández‐Cadenas I, Ribó M, Delgado P, Rubiera M, Penalba A, Rovira A, Montaner J. Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis. Stroke 39: 1456‐1463, 2008.
 10.Arnoldussen IAC, Kiliaan AJ, Gustafson DR. Obesity and dementia: Adipokines interact with the brain. Eur Neuropsychopharmacol 24: 1982‐1999, 2014.
 11.Aubin K, Safoine M, Proulx M, Audet‐Casgrain MA, Côté JF, Têtu FA, Roy A, Fradette J. Characterization of in vitro engineered human adipose tissues: Relevant adipokine secretion and impact of TNF‐α. PLoS One 10: e0137612, 2015.
 12.Baek K, Hwang HR, Park HJ, Kwon A, Qadir AS, Ko SH, Woo KM, Ryoo HM, Kim GS, Baek JH. TNF‐α upregulates sclerostin expression in obese mice fed a high‐fat diet. J Cell Physiol 229: 640‐650, 2014.
 13.Bajou K, Maillard C, Jost M, Lijnen RH, Gils A, Declerck P, Carmeliet P, Foidart JM, Noel A. Host‐derived plasminogen activator inhibitor‐1 (PAI‐1) concentration is critical for in vivo tumor angiogenesis and growth. Oncogene 23: 6986‐6990, 2004.
 14.Belalcazar LM, Ballantyne CM, Lang W, Haffner SM, Rushing J, Schwenke DC, Pi‐Sunyer FX, Tracy RP, the Lood AHEAD (Action for Health in Diabetes) Research Group. Metabolic factors, adipose tissue, and plasminogen activator inhibitor‐1 levels in type 2 diabetes. Findings from the look AHEAD study. Arterioscler Thromb Vasc Biol 31: 1689‐1695, 2011.
 15.Birdane A, Haznedaroğlu IC, Bavbek N, Koşar A, Büyükaşik Y, Ozcebe O, Dündar SV, Kirazli S. The plasma levels of prostanoids and plasminogen activator inhibitor‐1 in primary and secondary thrombocytosis. Clin Appl Thromb Hemost 11: 197‐201, 2005.
 16.Bobbert P, Eisenreich A, Weithauser A, Schultheiss HP, Rauch U. Leptin and resistin induce increased procoagulability in diabetes mellitus. Cytokine 56: 332‐337, 2011.
 17.Bojou K, Herkenne S, Thijssen VL, D'Amico S, Nguyen NQ, Bouché A, Tabruyn S, Srahna M, Carabin JY, Nivelles O, Paques C, Cornelissen I, Lion M, Noel A, Gils A, Vinckier S, Declerck PJ, Griffioen AW, Dewerchin M, Martial JA, Carmeliet P, Struman I. PAI‐1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin. Nat Med 20: 741‐751, 2014.
 18.Bremer AA, Devaraj S, Afify A, Jialal I. Adipose tissue dysregulation in patients with metabolic syndrome. J Clin Endocrinol Metab 96: E1782‐E1788, 2011.
 19.Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obesity 2013: 393192, 2013.
 20.Cale JM, Li SH, Warnock M, Su EJ, North PR, Sanders KL, Puscau MM, Emal CD, Lawrence DA. Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor‐1. J Biol Chem 285: 7892‐7902, 2010.
 21.Carmeliet P, Stassen JM, Schoonjans L, Ream B, van den Oord JJ, De Mol M, Mulligan RC, Collen D. Plasminogen activator inhibitor‐1 gene deficient mice. II. Effects on hemostasis, thrombosis and thrombolysis. J Clin Invest 92: 2756‐2760, 1993.
 22.Castrogiovanni D, Alzamendi A, Ongaro L, Giovambattista A, Gaillard RC, Spinedi E. Fructose rich diet‐induced high plasminogen activator inhibitor‐1 (PAI‐1) production in the adult female rat: Protective effect of progesterone. Nutrients 4: 1137‐1150, 2012.
 23.Chan JC, Duszczyszyn DA, Castellino FJ, Ploplis VA. Accelerated skin wound healing in plasminogen activator inhibitor‐1‐deficient mice. Am J Pathol 159: 1681‐1688, 2001.
 24.Chen S, Okahara F, Osaki N, Shimotoyodome A. Increased GIP signaling induces adipose inflammation via a HIF‐1α‐dependent pathway and impairs insulin sensitivity in mice. Am J Physiol Endocrinol Metab 308: E414‐E425, 2015.
 25.Chen Y, Billadello JJ, Schneider DJ. Identification and localization of a fatty acid response region in the human plasminogen activator inhibitor‐1 gene. Arterioscler Thromb Vasc Biol 20: 2696‐2701, 2000.
 26.Coelho MC, Oliveira T, Fernandes R. Biochemistry of adipose tissue: An endocrine organ. Arch Med Sci 2: 191‐200, 2013.
 27.Coelho MC, Santos CV, Vieira Neto L, Gadelha MR. Adverse effects of glucocorticoids: Coagulopathy. Eur J Endocrinol 173: 11‐21, 2015.
 28.Conde J, Scotece M, Gómez R, López V, Gómez‐Reino JJ, Lago F, Gualillo O. Adipokines: Biofactors from white adipose tissues. A complex hub among inflammation, metabolism, and immunity. Biofactors 37: 413‐420, 2011.
 29.Copland IB, Lord‐Dufour S, Cuerquis J, Coutu DL, Annabi B, Wang E, Galipeau J. Improved autograft survival of mesenchymal stromal cells by plasminogen activator inhibitor I inhibition. Stem Cells 27: 467‐477, 2009.
 30.Correia ML, Haynes WG. A role of plasminogen activator inhibitor‐1 in obesity: From Pie to PAI? Arterioscler Thromb Vasc Biol 26: 2183‐2185, 2006.
 31.Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360: 1509‐1517, 2009.
 32.Czekay RP, Loskutoff DJ. Plasminogen activator inhibitors regulate cell adhesion through a uPAR‐dependent mechanism. J Cell Physiol 220: 655‐663, 2009.
 33.Czekay RP, Wilkins‐Port CE, Higgins SP, Freytag J, Overstreet JM, Klein RM, Higgins CE, Samarakoon R, Higgins PJ. PAI‐1: An integrator of cell signaling and migration. Int J Cell Biol 2011: 562481, 2011.
 34.Daci E, Everts V, Torrekens S, Van Herck E, Tigchelaar‐Gutterr W, Bouillon R, Carmeliet G. Increased bone formation in mice lacking plasminogen activators. J Bone Miner Res 18: 1167‐1176, 2003.
 35.Daci E, Verstuyf A, Moermans K, Bouillon R, Carmeliet G. Mice lacking the plasminogen activator inhibitor 1 are protected from trabecular bone loss induced by estrogen deficiency. J Bone Miner Res 15: 1510‐1516, 2000.
 36.Darmon P, Dadoun F, Boullu‐Ciocca S, Grino M, Alessi MC, Dutour A. Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity. Am J Physiol Endocrinol Metab 291: E995‐E1002, 2006.
 37.de Castro J, Sevillano J, Marciniak J, Rodriguez R, Gonzalez‐Martin C, Viana M, Eun‐suk OH, de Mouzon SH, Herrera E, Ramos MP. Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy. Endocrinology 152: 4094‐4105, 2011.
 38.Deligeoroglou E, Vrachnis N, Athanasopoulos N, Iliodromiti Z, Sifakis S, Iliodromiti S, Siristatidis C, Creatsas G. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol Endocrinol 28: 974‐978, 2012.
 39.Devy L, Blacher S, Grignet‐Debrus C, Bajou K, Masson V, Gerard RD, Gils A, Carmeliet G, Carmeliet P, Declerck PJ, Nöel A, Foidart JM. The pro‐ or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J 16: 147‐154, 2002.
 40.Dimova EY, Kietzmann T. Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor‐1 (PAI‐1) expression: Lessons from the liver. Thromb Haemost 100: 992‐1006, 2008.
 41.DiMusto PD, Lu G, Ghosh A, Roelofs KJ, Su G, Zhao Y, Lau CL, Sadiq O, McEvoy B, Laser A, Diaz JA, Wakefield TW, Henke PK, Eliason JL, Upchurch GR, Jr. Increased PAI‐1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model. Am J Physiol Heart Circ Physiol 302: H1378‐H1386, 2012.
 42.Dzhoyashvili NA, Egimenko AY, Kochegura TN, Kalinina NI, Koptelova NV, Sukhareva OY, Shestakova MV, Akchurin RS, Tkachuk VA, Parfyonova YV. Disturbed angiogenic activity of adipose‐derived stromal cells obtained from patients with coronary artery disease and diabetes mellitus type 2. J Tansl Med 12: 337, 2014.
 43.Ebrahimian TG, Squiban C, Roque T, Lugo‐Martinez H, Hneino M, Buard V, Gourmelon P, Benderitter M, Milliat F, Tamarat R. Plasminogen activator inhibitor‐1 controls bone marrow‐derived cells therapeutic effect through MMP9 signaling: Role in physiological and pathological wound healing. Stem Cells 30: 1436‐1446, 2012.
 44.Eckel RH, Alberti KGMM, Grundy SM, Zimmer PZ. The metabolic syndrome. Lancet 375: 181‐183, 2010.
 45.Efimenko A, Dzhoyashvili N, Kalinina N, Kochegura T, Akchurin R, Tkachuk V, Parfyonova Y. Adipose‐derived mesenchymal stromal cells from aged patients with coronary artery disease keep mesenchymal stromal cell properties but exhibit characteristics of aging and have impaired angiogenic potential. Stem Cells Transl Med 3: 32‐41, 2014.
 46.Eitzman DT, Westrick RJ, Nabel EG, Ginsburg D. Plasminogen activator inhibitor‐1 and vitronectin promote vascular thrombosis in mice. Blood 95: 577‐580, 2000.
 47.Eitzman DT, Westrick RJ, Xu Z, Tyson J, Ginsburg D. Plasminogen activator inhibitor‐1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Blood 96: 4212‐4215, 2000.
 48.Eksteen P, Pieters M, de Lange Z, Kruger HS. The association of clot lysis time with total obesity is partly independent from the association of PAI‐1 with central obesity in African adults. Thromb Res 136: 415‐421, 2015.
 49.Ekström M, Liska J, Eriksson P, Sverremark‐Ekström E, Tornvall P. Stimulated in vivo synthesis of plasminogen activator inhibitor‐1 in human adipose tissue. Thromb Haemost 108: 485‐492, 2012.
 50.Elzi DJ, Lai Y, Song M, Hakala K, Weintraub ST, Shiio Y. Plasminogen activator inhibitor 1‐insulin‐like growth factor binding protein 3 cascade regulates stress‐induced senescence. Proc Natl Acad Sci U S A 109: 12052‐12057, 2012.
 51.Erem C, Nuhoglu I, Yilmaz M, Kocak M, Demirel A, Ucuncu O, Onder Ersoz H. Blood coagulation and fibrinolysis in patients with Cushing's syndrome: Increased plasminogen activator inhibitor‐1, decreased tissue factor pathway inhibitor, and unchanged thrombin‐activatable fibrinolysis inhibitor levels. J Endocrinol Invest 32: 169‐174, 2009.
 52.Eren M, Boe AE, Murphy SB, Place AT, Nagpal V, Morales‐Nebreda L, Urich D, Quaggin SE, Budinger GR, Mutlu GM, Miyata T, Vaughan DE. PAI‐1‐regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc Natl Acad Sci USA 111: 7090‐7095, 2014.
 53.Eren M, Painter CA, Atkinson JB, Declerck PJ, Vaughan DE. Age‐dependent spontaneous coronary arterial thrombosis in transgenic mice that express a stable form of human plasminogen activator inhibitor‐1. Circulation 106: 491‐496, 2002.
 54.Erickson LA, Fici GJ, Lund JE, Boyle TP, Polites HG, Marotti KR. Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor‐1 gene. Nature 346: 74‐76, 1990.
 55.Eriksson P, Van Harmelen V, Hoffstedt J, Lundquist P, Vidal H, Stemme V, Hamsten A, Amer P, Reynisdottir S. Regional variation in plasminogen activator inhibitor‐1 expression in adipose tissue from obese individuals. Thromb Haemost 83: 545‐548, 2000.
 56.Esterson YB, Kishore P, Koppaka S, Li W, Zhang K, Tonelli J, Lee DE, Kehlenbrink S, Lawrence S, Crandall J, Barzilai N, Hawkins M. Fatty acid‐induced production of plasminogen activator inhibitor‐1 by adipose macrophages is greater in middle‐aged versus younger adult participants. J Gerontol A Biol Sci Med Sci 67: 1321‐1328, 2012.
 57.Fasshauer M, Klein J, Kralisch S, Klier M, Lossner U, Bluher M, Paschke R. Monocyte chemoattractant protein 1 expression is stimulated by growth hormone and interleukin‐6 in 3T3‐L1 adipocytes. Biochem Biophys Res Commun 317: 598‐604, 2004.
 58.Fei J, Cook C, Blough E, Santanam N. Age and sex mediated changes in epicardial fat adipokines. Atherosclerosis 212: 4880494, 2010.
 59.Ferroni P, Roselli M, Portarena I, Formica V, Riondino S, LA Farina F, Costarelli L, Melino A, Massimiani G, Cavaliere F, Palmirotta R, Guadagni F. Plasma plasminogen activator inhibitor‐1 (PAI‐1) levels in breast cancer‐relationship with clinical outcome. Anticancer Res 34: 1153‐1161, 2014.
 60.Freemerman AJ, Johnson AR, Sacks GN, Milner JJ, Kirk EL, Troester MA, Macintyre AN, Goraksha‐Hicks P, Rathmell JC, Makowski L. Matbolic reprogramming of macrophages. glucose transporter 1 (GLUT1)‐mediated glucose metabolism drives a proinflammatory phenotype. J Biol Chem 289: 7884‐7896, 2014.
 61.Friederich PW, Levi M, Biemond BJ, Charlton P, Templeton D, van Zonneveld AJ, Bevan P, Pannekoek H, ten Cate JW. Novel low‐molecular‐weight inhibitor of PAI‐1 (XR5118) promotes endogenous fibrinolysis and reduces postthrombolysis thrombus growth in rabbits. Circulation 96: 916‐921, 1997.
 62.Garg N, Fay WP. Plasminogen activator inhibitor‐1 and restenosis. Curr Drug Targets 8: 1003‐1006, 2007.
 63.Gomez‐Hernandez A, Otero YF, de las Heras N, Escribano O, Cachoofeiro V, Lahera V, Benito M. Brown fat lipoatrophy and increased visceral adiposity through a concerted adipocytokines overexpression induces vascular insulin resistance and dysfunction. Endocrinology 153: 1242‐1255, 2012.
 64.Grant MB, Ellis EA, Caballero S, Mames RN. Plasminogen activator inhibitor‐1 overexpression in non‐proliferating diabetic retinopathy. Exp Eye Res 63: 233‐244, 1996.
 65.Halamkova J, Kiss I, Pavlovsky Z, Jarkovsky J, Tomasek J, Tucek S, Hanakova L, Moulis M, Cech Z, Zavrelova J, Penka M. Clinical relevance of uPA, uPAR, PAI 1 and PAI 2 tissue expression and plasma PAI 1 level in colorectal carcinoma patients. Hepatogastroenterology 58: 1918‐1925, 2011.
 66.Hamsten A, de Faire U, Walldius G, Dahlén G, Szamosi A, Landou C, Blombäck M, Wiman B. Plasminogen activator inhibitor in plasma‐risk factor for recurrent myocardial infarction. Lancet 2: 3‐9, 1987.
 67.Hayashi M, Takeshita K, Uchida Y, Yamamoto K, Kikuchi R, Nakayama T, Nomura E, Cheng XW, Matsushita T, Nakamura S, Murohara T. Angiotensin II receptor blocker ameliorates stress‐induced adipose tissue inflammation and insulin resistance. PLoS One 9: e116163, 2014.
 68.Henman JK, Elokdah H, Leal M, Ji A, Friedrich GS, Morgan GA, Swillo RE, Antrilli TM, Hreha A, Crandall DL. Evaluation of PAI‐039 [{1‐benzyl‐5‐[4‐(trifluoromethoxy)phenyl]‐1H‐indol‐3‐yl}(oxo)acetic acid], a novel plasminogen activator inhibitor‐1, in a canine model of coronary artery thrombosis. J Pharmacol Exp Ther 314: 710‐716, 2005.
 69.Herz J, Strickland DK. LRP: A multifunctional scavenger and signaling receptors. J Clin Invest 108: 779‐784, 2001.
 70.Hiessing B, Lund LR, Akiyama H, Ohki M, Morita Y, Rømer J, Nakauchi H, Okumura K, Ogawa H, Werb Z, Danø K, Hattori K. The plasminogen fibrinolytic pathway is required for hematopoietic regeneration. Cell Stem Cell 1: 658‐670, 2007.
 71.Hillengrand A, Weiss M, Knippschild U, Wolf AM, Huber‐Lang M. Sepsis‐induced adipokine change with regard to insulin resistance. Int J Inflam 2012: 972368, 2012.
 72.Hoekstra T, Geleijnse JM, Schouten EG, Kluft C. Plasminogen activator inhibitor‐type 1: Its plasma determinants and relation with cardiovascular risk. Thromb Haemost 91: 861‐872, 2004.
 73.Hsu CL, Lin YL, Ho CT, Yen GC. The inhibitory effect of pterostilbene on inflammatory responses during the interaction of 3T3‐L1 adipocytes and RAW 264.7 macrophages. J Agric Food Chem 61: 602‐610, 2013.
 74.Huang W, Vayalil P, Miyata T, Hagwood J, Liu RM. Therapeutic value of small molecule inhibitor to plasminogen activator inhibitor‐1 for lung fibrosis. Am J Respir Cell Mol Biol 46: 87‐95, 2012.
 75.Ibrahim AA, Yahata T, Onizuka M, Dan T, Van Ypersele De Strihou C, Miyata T, Ando K. Inhibition of plasminogen activator inhibitor type‐1 activity enhances rapid and sustainable hematopoietic regeneration. Stem Cells 32: 946‐958, 2014.
 76.Ito S, Iwaki S, Koike K, Yuda Y, Nagasaki A, Ohkawa R, Yatomi Y, Furumoto T, Tsutsui H, Sobel BE, Fujii S. Increased plasma sphingosine‐1‐phosphate in obese individuals and its capacity to increase the expression of plasminogen activator inhibitor‐1 in adipocytes. Coron Artery Dis 24: 642‐650, 2013.
 77.Izuhara Y, Takahashi S, Nangaku M, Takizawa S, Ishida H, Kurokawa K, van Ypersele de Strihou C, Hirayama N, Miyata T. Inhibition of plasminogen activator inhibitor‐1: Its mechanism and effectiveness on coagulation and fibrosis. Arterioscler Thromb Vasc Biol 28: 672‐677, 2008.
 78.Janand‐Delenne B, Chagnaud C, Raccah D, Alessi MC, Juhan‐Vague I, Vague P. Visceral fat as a main determinant of plasminogen activator inhibitor 1 level in women. Int J Obes Relat Metab Disord 22: 312‐317, 1998.
 79.Jansen HJ, Vervoort GM, van der Graaf M, Stienstra R, Tack CJ. Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients. Clin Endocrinol (Pxf) 79: 661‐666, 2013.
 80.Juhan‐Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation 94: 2057‐2063, 1996.
 81.Kalupahana NS, Claycombe K, Newman SJ, Stewart T, Siriwardhana N, Matthan N, Lichtenstein AH, Moustaid‐Moussa N. Eicosapentaenpooic acid prevents and reverses insulin resistance in high‐fat diet‐induced obese mice via modulation of adipose tissue inflammation. J Nutr 140: 1915‐1922, 2010.
 82.Kanuri G, Landmann M, Priebs J, Spruss A, Löscher M, Ziegenhardt D, Röhl C, Degen C, Bergheim I. Moderate alcohol consumption diminishes the development of non‐alcoholic fatty liver disease (NAFLD) in ob/ob mice. Eur J Nutr 55: 1153‐1164, 2016.
 83.Karbiener M, Neuhold C, Opriessnig P, Prokesch A, Bogner‐Strauss JG, Scheideler M. MicroRNA‐30c promotes human adipocyte differentiation and co‐represses PAI‐1 and ALK2. RNA Biol 8: 850‐860, 2011.
 84.Kawao N, Tamura Y, Horiuchi Y, Okumoto K, Yano M, Okada K, Matsuo O, Kaji H. The tissue fibrinolytic system contributes to the induction of macrophage function and CCL3 during bone repair in mice. PLoS One 10: e0123982, 2015.
 85.Kawao N, Tamura Y, Okumoto K, Yano M, Okada K, Matsuo O, Kaji H. Plasminogen plays a crucial role in bone repair. J Bone Miner Res 28: 1561‐1574, 2013.
 86.Kawao N, Tamura Y, Okumoto K, Yano M, Okada K, Matsuo O, Kaji H. Tissue‐type plasminogen activator deficiency delays bone repair: Roles of osteoblastic proliferation and vascular endothelial growth factor. Am J Physiol Endocrinol Metab 307: E278‐E288, 2014.
 87.Kim MS, Ryabets‐Lienhard A, Dao‐Tran A, Mittelman SD, Gilsanz V, Schrager SM, Geffner ME. Increased abdominal adiposity in adolescents and young adults with classical congenital adrenal hyperplasia due to 21‐hydroxylase deficiency. J Clin Endocrinol Metab 100: E1153‐E1159, 2015.
 88.Kishore P, Li W, Tonelli J, Lee DE, Koppaka S, Zhang K, Lin Y, Kehlenbrink S, Scherer PE, Hawkins M. Adipocyte‐derived factors potentiate nutrient‐induced production of plasminogen activator inhibitor‐1 by macrophages. Sci Transl Med 2: 20ral5, 2010.
 89.Kitamura H, Kimura S, Shimamoto Y, Okabe J, Ito M, Miyamoto T, Naoe Y, Kikuguchi C, Meek B, Toda C, Okamoto S, Kanehira K, Hase K, Watarai H, Ishizuka M, El‐Osta A, Ohara O, Miyoshi I. Ubiquitin‐specific protease 2‐69 in macrophages potentially modulates metainflammation. FASEB J 27: 4940‐4953, 2013.
 90.Koeck ES, Iordanskaia T, Sevilla S, Ferrante SC, Hubal MJ, Freishtat RJ, Nadler EP. Adipocyte exosomes induce transforming growth factor β pathway dysregulation in hepatocytes: A novel paradigm for obesity‐related liver disease. J Surg Res 192: 268‐275, 2014.
 91.Koh KK, Han SH, Shin MS, Ahn JY, Lee Y, Shin EK. Significant differential effects of lower doses of hormone therapy or tibolone on markers of cardiovascular disease in postmenopausal women: A randomized, double‐blind, crossover study. Eur Heart J 26: 1362‐1368, 2005.
 92.Koh TJ, Bryer SC, Pucci AM, Sisson TH. Mice deficient in plasminogen activator inhibitor‐1 have improved skeletal muscle regeneration. Am J Physiol Cell Physiol 289: C217‐C223, 2005.
 93.Komiyama S, Aoki D, Saitoh E, Komiyama M, Udagawa Y. Biological significance of plasminogen activator inhibitor‐1 expression in ovarian clear cell carcinoma. Eur J Gynaecol Oncol 32: 611‐614, 2011.
 94.Konkle BA, Schuster SJ, Kelly MD, Harjes K, Hassett DE, Bohrer M, Tavassoli M. Plasminogen activator inhibitor‐1 messenger RNA expression is induced in rat hepatocytes in vivo by dexamethasone. Blood 79: 2636‐2642, 1992.
 95.Konstantinides S, Schäfer K, Thinnes T, Loskutoff DJ. Plasminogen activator inhibitor‐1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice. Circulation 103: 576‐583, 2001.
 96.Konstantinides S, Schäfer K, Loskutoff DJ. Do PAI‐1 and vitronectin promote or inhibit neointima formation? The exact role of the fibrinolytic system in vascular remodeling remains uncertain. Arteriocler Thromb Vasc Biol 22: 1943‐1945, 2002.
 97.Kortlever RM, Higgins PJ, Bernards R. Plasminogen activator inhibitor‐1 is a critical downstream of p53 in the induction of replicative senescence. Nat Cell Biol 8: 877‐884, 2006.
 98.Krause MP, Moradi J, Nissar AA, Riddell MC, Hawke TJ. Inhibition of plasminogen activator inhibitor‐1 restores skeletal muscle regeneration in untreated type‐1 diabetic mice. Diabetes 60: 1964‐1972, 2011.
 99.Kuniyasu A, Tokunaga M, Yamamoto T, Inoue S, Obama K, Kawahara K, Nakayama H. Oxidized LDL and lysophosphatidylcholine stimulate plasminogen activator inhibitor‐1 expression through reactive oxygen species generation and ERK1/2 activation in 3T3‐L1 adipocytes. Biochim Biophys Acta 1811: 153‐162, 2011.
 100.Łabuzek K, Bułdak Ł, Duława‐Bułdak A, Bielecka A, Krysiak R, Madej A, Okopień B. Atrovastatin and fenofibric acid differently affect the release of adipokines in the visceral and subcutaneous cultures of adipocytes that were obtained from patients with and without mixed dyslipidemia. Pharmacol Rep 63: 1124‐1136, 2011.
 101.Lambers JW, Cammenga M, Konig BW, Mertens K, Pannekock H, van Mourik JA. Activation of human endothelial cell‐type plasminogen activator inhibitor (PAI‐1) by negatively charged phospholipids. J Biol Chem 262: 17492‐17496, 1987.
 102.Li Y, Liu L, Wang B, Wang J, Chen D. Simple steatosis is a more relevant source of serum inflammatory markers than omental adipose tissue. Clin Res Hepatol Gastroenterol 38: 46‐54, 2014.
 103.Liang X, Kanjanabunch T, Mao S, Hao C, Tang Y, Declerck PJ, Hasty AH, Wasserman DH, Fogo AB, Ma LJ. Plasminogen activator inhibitor‐1 modulates adipocyte differentiation. Am J Physiol Endocrinol Metab 290: E103‐E113, 2006.
 104.Lijnen HR. Pleiotropic functions of plasminogen activator inhibitor‐1. J Thromb Haemost 3: 35‐45, 2005.
 105.Lijnen HR, Maquoi E, Morange P, Voros G, Van Hoef B, Kopp F, Collen D, Juhan‐Vague I, Alessi MC. Nutritionally induced obesity is attenuated in transgenic mice overexpression plasminogen activator inhibitor‐1. Arterioscler Thromb Vasc Biol 23: 78‐4, 2003.
 106.Lijnen HR, Van Hul M, Hemmeryckx B. Caloric restriction improves coagulation and inflammation profile in obese mice. Thromb Res 129: 74‐79, 2012.
 107.Lim S, Meigs JB. Ectopic fat and cardiometabolic and vascular risk. Int J Cardiol 169: 166‐176, 2013.
 108.Liu YX. Plasminogen activator/plasminogen activator inhibitors in ovarian physiology. Front Biosci 9: 3356‐3373, 2004.
 109.López‐Alemany R, Redondo JM, Nagamine Y, Muñoz‐Cánoves P. Plasminogen activator inhibitor type‐1 inhibits insulin signaling by competing with αVβ3 integrin for vitronectin binding. Eur J Biochem 270: 814‐821, 2003.
 110.Loskutiff DJ, Linders M, Keijer J. Structure of the human plasminogen activator inhibitor 1 gene: Nonrandom distribution of introns. Biochemistry 26: 3763‐3768, 1987.
 111.Loskutiff DJ, van Mourik JA, Erickson LA, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells. Proc Natl Acad Sci USA 80: 2956‐2960, 1983.
 112.Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor‐1. Diabetes 53: 336‐346, 2004.
 113.Manolescu B, Stoian I, Atanasiu V, Busu C, Lupescu O. The role of adipose tissue in uremia‐related insulin resistance. Nephrology (Carlton) 13: 622‐628, 2008.
 114.Mao L, Kawao N, Tamura Y, Okumoto K, Okada K, Yano M, Matsuo O, Kaji H. Plasminogen activator inhibitor‐1 is involved in impaired bone repair associated with diabetes in female mice. PLoS One 9: e92686, 2014.
 115.Masqulo DC, de Piano A, Sanches PL, Corgosinho FC, Campos RM, Carnier J, da Silva PL, Caranti DA, Tock L, Oyama LM, Oller do Nascimento CM, de Mello MT, Tufik S, Dâmaso AR. The effect of weight loss magnitude on pro‐/anti‐inflammatory adipokines and carotid intima‐media thickness in obese adolescents engaged in interdisciplinary weight loss therapy. Clin Endocrinol (Oxf) 79: 55‐64, 2013.
 116.Mathieu P, Lemieux I, Després JP. Obesity, inflammation, and cardiovascular risk. Clin Pharmacol Ther 87: 407‐416, 2010.
 117.Mauro CR, Ilonzo G, Nguyen BT, Yu P, Tao M, Gao I, Seidman MA, Nguyen LL, Ozaki CK. Attenuated adiposopathy in perivascular adipose tissue compared with subcutaneous human adipose tissue. Am J Surg 206: 241‐244, 2013.
 118.Maurovich‐Horvat P, Kallianos K, Engel LC, Szymonifka J, Schlett CL, Koenig W, Hoffmann U, Truong QA. Relationship of thoracic fat depots with coronary atherosclerosis and circulating inflammatory biomarkers. Obesity 23: 1178‐1184, 2015.
 119.Meas T, Deghmoun S, Chevenne D, Gaborit B, Alessi MC, Lévy‐Marchal C. Plasminogen activator inhibitor type‐1 is an independent marker of metabolic disorders in young adults born small for gestational age. J Thromb Haemost 8: 2608‐2613, 2010.
 120.Meltzer ME, Lisman T, de Groot PG, Meijers JC, le Cessie S, Doggen CJ, Rosendaal FR. Venous thrombosis risk associated with plasma fibrinolysis is explained by elevated plasma levels of TAFI and PAI‐1. Blood 116: 113‐121, 2010.
 121.Mendivil CO, Robles‐Osorio L, Horton ES, Hamdy O, Caballero AE. Young Hispanics at risk of type 2 diabetes display endothelial activation, subclinical inflammation and alterations of coagulation and fibrinolysis. Diabetol Metab Synd 5: 37, 2013.
 122.Miao H, Zhang Y, Lu Z, Liu Q, Gan L. FOXO1 involvement in insulin resistance‐related pro‐inflammatory cytokine production in hepatocytes. Inflamm Res 61: 349‐358, 2012.
 123.Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 8: 738‐742, 2002.
 124.Molinar‐Toribio E, Pérez‐Jiménez J, Ramos‐Romero S, Lluís L, Sánchez‐Martos V, Taltavull N, Romeu M, Pazos M, Méndez L, Miranda A, Cascante M, Medina I, Torres JL. Cardiovascular disease‐related parameters and oxidative stress in SHROB rats, a model for metabolic syndrome. PLoS One 9: e104637, 2014.
 125.Moor E, Blombäck M, Silveira A, Wiman B, Cederlund K, Bergstrand L, Ivert T, Rydén L, Hamsten A. Haemostatic function in patients undergoing coronary artery bypass grafting: Preoperative perturbations and relations to saphenous vein graft closure. Thromb Res 98: 39‐49, 2000.
 126.Morange PE, Lijnen HR, Alessi MC, Kopp F, Collen D, Juhan‐Vague I. Influence of PAI‐1 on adipose tissue growth and metabolic parameters in a murine model of diet‐induced obesity. Atrerioscler Thromb Vasc Biol 20: 1150‐1154, 2000.
 127.Morikawa K, Hanada H, Hirota K, Nonaka M, Ikeda C. All‐trans retinoic acid displays multiple effects on the growth, lipogenesis and adipokine gene expression of AML‐I preadipocyte cell line. Cell Biol Int 37: 36‐46, 2013.
 128.Mottillo EP, Shen XJ, Granneman JG. β3‐Adrenergic receptor induction of adipocyte inflammation requires lipolytic activation of stress kinase p38 and JNK. Biochim Biophys Acta 1801: 1048‐1055, 2010.
 129.Mutch NJ, Wilson HM, Booth NA. Plasminogen activator inhibitor‐1 and haemostasis in obesity. Proc Nutr Soc 60: 341‐347, 2001.
 130.Naderi J, Bernreuther C, Grabinski N, Putman CT, Henkel B, Bell G, Glatzel M, Sultan KR. Plasminogen activator inhibitor type 1 up‐regulation is associated with skeletal muscle atrophy and associated fibrosis. Am J Pathol 175: 763‐771, 2009.
 131.Nguyen Dinh Cat A, Briones AM, Callera GE, Yogi A, He Y, Montezano AC, Touyz RM. Adipocyte‐derived factors regulate vascular smooth muscle cells through mineralcorticoid and glucocorticoid receptors. Hypertension 58: 479‐488, 2011.
 132.Nicholas SB, Aguiniga E, Ren Y, Kim J, Wong J, Govindarajan N, Noda M, Wang W, Kawano Y, Collins A, Hsueh WA. Plasminogen activator inhibitor‐1 deficiency retards diabetic nephropathy. Kidney Int 67: 1297‐1307, 2005.
 133.Nishi T, Shimizu N, Hiramoto M, Sato I, Yamaguchi Y, Hasegawa M, Aizawa S, Tanaka H, Kataoka K, Watanabe H, Handa H. Spatial redox regulation of a critical cystein residue of NF‐κB in vivo. J Biol Chem 277: 44548‐44556, 2002.
 134.Niwa M, Numaguchi Y, Ishii M, Kuwahata T, Kondo M, Shibata R, Miyata K, Oike Y, Murohara T. IRAP deficiency attenuates diet‐induced obesity in mice through increased energy expenditure. Biochem Biophys Res Commun 457: 12‐18, 2015.
 135.Nordstrom SM, Carleton SM, Carson WL, Eren M, Philips CL, Vaughan DE. Transgenic over‐expression of plasminogen activator inhibitor‐1 results in age‐dependent and gender‐specific increases in bone strength and mineralization. Bone 41: 995‐1004, 2007.
 136.Ohkura N, Shirakura M, Nakatani E, Oishi K, Atsumi G. Associations between plasma PAI‐1 concentrations and its expressions in various organs in obese model mice. Thromb Res 130: e301‐e304, 2012.
 137.Oishi K. Plasminogen activator inhibitor‐1 and the circadian clock in metabolic disorders. Clin Exp Hypertens 31: 208‐219, 2009.
 138.Oishi K, Ohkura N, Kasamatsu M, Fukushima N, Shirai H, Matsuda J, Horie S, Ishida N. Tissue‐specific augmentation of circadian PAI‐1 expression in mice with streptozotocin‐induced diabetes. Thromb Res 114: 129‐135, 2004.
 139.Oishi K, Ohkura N, Matsuda J, Ishida N. Food deprivation induces adipose plasminogen activator inhibitor‐1 (PAI‐1) expression without accumulation of plasma PAI‐1 in genetically obese and diabetic db/db mice. Thromb Haemost 98: 864‐870, 2007.
 140.Palomo IG, Gutiérrez CL, Alarcón ML, Jaramillo JC, Segovia FM, Leiva EM, Mujica VE, Icaza GN, Díaz NS, Moore‐Carrasco R. Increased concentration of plasminogen activator inhibitor‐1 and fibrinogen in individuals with metabolic syndrome. Mol Med Report 2:253‐257, 2009.
 141.Pan Y, Shu JL, Gu HF, Zhou DC, Liu XL, Qiao QY, Fu SK, Gao FH, Jin HM. Erythropoietin improves insulin resistance via the regulation of its receptor‐mediated signaling pathways in 3T3‐L1 adipocytes. Mol Cell Endocrinol 367: 116‐123, 2013.
 142.Pardina E, Ferrer R, Rivero J, Baena‐Fustegueras JA, Lecube A, Fort JM, Vargas V, Catalán R, Peinado‐Onsurbe J. Alterations in the common pathway of coagulation during weight loss induced by gastric bypass in severely obese patients. Obesity (Silver Spring) 20: 1048‐1056, 2012.
 143.Park KS. Aucubin, a naturally occurring iridoid glycoside inhibits TNF‐α‐induced inflammatory responses through suppression of NF‐κB activation in 3T3‐L1 adipocytes. Cytokine 62: 407‐412, 2013.
 144.Pralong G, Calandra T, Glauser MP, Schellekens J, Verhoef J, Bachmann F, Kruithof EK. Plasminogen activator inhibitor‐1: A new prognostic marker in septic shock. Thromb Haemost 61: 459‐462, 1989.
 145.Rega G, Kaun C, Weiss TW, Demyanets S, Zorn G, Kastl SP, Steiner S, Seidinger D, Kopp CW, Frey M, Roehle R, Maurer G, Huber K, Wojta J. Inflammatory cytokines interleukin 6 and oncostatin M induce plasminogen activator inhibitor‐1 in human adipose tissue. Circulation 111: 1938‐1945, 2005.
 146.Rundle GH, Wang X, Wergedal JE, Mohan S, Lan KH. Fracture healing in mice deficient in plasminogen activator inhibitor‐1. Caclif Tissue Int 83: 276‐284, 2008.
 147.Saad F. Androgen therapy in men with testosterone deficiency: Can testosterone reduce the risk of cardiovascular disease? Diabetes Metab Res Rev 28(Suppl 2): 52‐59, 2012.
 148.Sacks HS, Fain JN. Human epicardial adipose tissue: A review. Am Heart J 153: 907‐917, 2007.
 149.Sakata T, Kario K. Antiplatelet therapy effectively reduces plasma plasminogen activator inhibitor‐1 levels. Atherosclerosis 214: 490‐491, 2011.
 150.Samad F, Yamamoto K, Loskutoff DJ. Distribution and regulation of plasminogen activator inhibitor‐1 in murine adipose tissue in vivo. Induction by tumor necrosis factor‐α and lipopolysaccharide. J Clin Invest 97: 37‐46, 1996.
 151.Sanchez‐Infantes D, White UA, Elks CM, Morrison RF, Gimble JM, Considine RV, Ferrante AW, Ravussin E, Stephens JM. Oncostatin M is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes. J Clin Endocrinol Metab 99: E217‐E225, 2014.
 152.Sawdey MS, Loskutoff DJ. Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. J Clin Invest 88: 161‐166, 1991.
 153.Sayer JW, Gutteridgs C, Syndercombe‐Court D, Wilkinson P, Timmis AD. Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: Effects of β‐adrenoreceptor blockers and angiotensin‐converting enzyme inhibitors. J Am Coll Cardiol 32: 1962‐1968, 1998.
 154.Schäfer K, Fujisawa K, Konstantinides S, Loskutoff DJ. Disruption of the plasminogen activator inhibitor‐1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob/ob mice. FASEB J 15: 1840‐1842, 2001.
 155.Schäfer K, Konstantinides S. Adipokines and cardiovascular disease. Clin Exp Pharmacol Physiol 38: 864‐871, 2011.
 156.Schäfer K, Müller K, Hecke A, Mounier E, Goebel J, Loskutoff DJ, Konstantinides S. Enhanced thrombosis in atherosclerosis‐prone mice is associated with increased arterial expression of plasminogen activator inhibitor‐1. Arterioscler Thromb Vasc Biol 23: 2097‐2103, 2003.
 157.Schneider DJ, Chen Y, Sobel BE. The effect of plasminogen activator inhibitor type 1 on apoptosis. Thromb Haemost 100: 1037‐1040, 2008.
 158.Scroyen I, Jacobs F, Cosemans L, De Geest B, Lijnen HR. Effects of plasminogen activator inhibitor‐1 on adipogenesis in vivo. Thromb Haemost 101: 388‐393, 2009.
 159.Seetoo DQ, Crower PJ, Russell PJ, Yang JL. Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer. J Surg Oncol 82: 184‐193, 2003.
 160.Seki T, Miyasu T, Noguchi T, Hamasaki A, Sasaki R, Ozawa Y, Okukita K, Declerck PJ, Ariga T. Reciprocal regulation of tissue‐type and urokinase‐type plasminogen activators in the differentiation of murine preadipocyte line 3T3‐L1 and the hormonal regulation of fibrinolytic factors in the mature adipocytes. J Cell Physiol 189: 72‐78, 2001.
 161.Shah C, Yang G, Lee I, Bielawski J, Hannun YA, Samad F. Protection from high fat diet‐induced increase in ceramide in mice lacking plasminogen activator inhibitor‐1. J Biol Chem 283: 13538‐13548, 2008.
 162.Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, Sata M. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 33: 1077‐1084, 2013.
 163.Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y. Enhanced expression of PAI‐1 in visceral fat: Possible contributor to vascular disease in obesity. Nat Med 2: 800‐803, 1996.
 164.Shiomi A, Kawao N, Yano M, Okada K, Tamura Y, Okumoto K, Matsuo O, Akagi M, Kaji H. α2‐Antiplasmin is involved in bone loss induced by ovariectomy in mice. Bone 79: 233‐241, 2015.
 165.Shirakawa J, Fujii H, Ohnuma K, Sato K, Ito Y, Kaji M, Sakamoto E, Koganei M, Sasaki H, Hagashima Y, Amo K, Aoki K, Morimoto C, Takeda E, Terauchi Y. Diet‐induced adipose tissue inflammation and liver steatosis are prevented by DPP‐4 inhibition in diabetic mice. Diabetes 60: 1246‐1257, 2011.
 166.Siklova‐Vitkova M, Klimcakova E, Polak J, Kovacova Z, Tencerova M, Rossmeislova L, Bajzova M, Langin D, Stich V. Adipose tissue secretion and expression of adipocyte‐produced and stromavascular fraction‐produced adipokines vary during multiple phases of weight‐reducing dietary intervention in obese women. J Clin Endocrinol Metab 97: E1176‐E1181, 2012.
 167.Simpson AJ, Booth NA, Moore NR, Bennett B. Distribution of plasminogen activator inhibitor (PAI‐1) in tissues. J Clin Pathol 44: 139‐143, 1991.
 168.Singh P, Peterson TE, Barber KR, Kuniyoshi FS, Jensen A, Hoffmann M, Shamsuzzaman AS, Somers VK. Leptin upregulates the expression of plasminogen activator inhibitor‐1 in human vascular endothelial cells. Biochem Biophys Res Commun 392: 47‐52, 2010.
 169.Skurk T, Hauner H. Obesity and impaired fibrinolysis: Role of adipose production of plasminogen activator inhibitor‐1. Int J Obes Relat Metab Disord 281: 357‐364, 2004.
 170.Sundaram S, Bukowski MR, Lie WR, Picklo MJ, Yan L. High‐fat diets containing different amounts of n3 and n6 polyunsaturated fatty acids modulate inflammatory cytokine production in mice. Lipids 51: 571‐582, 2016.
 171.Takeshita K, Hayashi M, Iino S, Kondo T, Inden Y, Iwase M, Kojima T, Hirai M, Ito M, Loskutoff DJ, Saito H, Murohara T, Yamamoto K. Increased expression of plasminogen activator inhibitor‐1 in cardiomyocytes contributes to cardiac fibrosis after myocardial infarction. Am J Pathol 164: 449‐456, 2004.
 172.Takeshita K, Yamamoto K, Ito M, Kondo T, Matsushita T, Hirai M, Kojima T, Nishimura M, Nabeshima Y, Loskutoff DJ, Saito H, Murohara T. Increased expression of plasminogen activator inhibitor‐1 with fibrin deposition in a murine model of aging, “Klotho” mouse. Semin Thromb Hemost 28: 545‐554, 2002.
 173.Tamura Y, Kawao N, Okada K, Yano M, Okumoto K, Matsuo O, Kaji H. Plasminogen activator inhibitor‐1 is involved in streptozotocin‐induced bone loss in female mice. Diabetes 62: 3170‐3179, 2013.
 174.Tamura Y, Kawao N, Yano M, Okada K, Matsuo O, Kaji H. Plasminogen activator inhibitor‐1 deficiency ameliorates insulin resistance and hyperlipidemia but not bone loss in obese female mice. Endocrinology 155: 1708‐1717, 2014.
 175.Tamura Y, Kawao N, Yano M, Okada K, Okumoto K, Chiba Y, Matsuo O, Kaji H. Role of plasminogen activator inhibitor‐1 in glucocorticoid‐induced diabetes and osteopenia in mice. Diabetes 64: 2194‐2206, 2015.
 176.Tan JT, McLennan SV, Williams PF, Rezaeizadeh A, Lo LW, Bonner JG, Twigg SM. Connective tissue growth factor/CCN‐2 is upregulated in epididymal and subcutaneous fat depots in a dietary‐induced obesity model. Am J Physiol Endocrinol Metab 304: E1291‐E1302, 2013.
 177.Tashiro Y, Nishida C, Sato‐Kusubata K, Ohki‐Koizumi M, Ishihara M, Sato A, Gritli I, Komiyama H, Sato Y, Dna T, Miyata T, Okumura K, Tomiki Y, Sakamoto K, Nakauchi H, Heissig B, Hattori K. Inhibition of PAI‐1 induces neutrophil‐driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice. Blood 119: 6382‐6393, 2012.
 178.Thogersen AM, Jansson JH, Boman K, Nilsson TK, Weinhall L, Huhtassari F, Hallmans G. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma proceed a first acute myocardial infarction in both men and women‐evidence for the fibrinolytic system as an independent primary risk factor. Circulation 98: 2241‐2247, 1998.
 179.Tjärnlund‐Wolf A, Brogren H, Lo EH, Wang X. Plasminogen activator inhihibitor‐1 and thrombotic cereberovascular diseases. Stroke 43: 2833‐2839, 2012.
 180.Tripathy D, Daniele G, Fiorentino TV, Perez‐Cadena Z, Chavez‐Velasquez A, Kamath S, Fanti P, Jenkinson C, Andreozzi F, Federici M, Gastaldelli A, DeFronzo RA, Folli F. Pioglitazone improves glucose metabolism and modulates skeletal muscle TIMP‐3‐TACE duad in type 2 diabetes mellitus: A randomized, double‐blind, placebo‐controlled, mechanistic study. Diabetologia 56: 2153‐2163, 2013.
 181.Trzeciak‐Ryczek A, Tokarz‐Deptula B, Niedzwiedzka‐Rystwej P, Deptula W. Adipose tissue‐component of the immune system. Cent Eur J Immunol 36: 95‐99, 2011.
 182.Uchida Y, Takeshita K, Yamamoto K, Kikuchi R, Nakayama T, Nomura M, Cheng XW, Egashira K, Matsushita T, Nakamura H, Murohara T. Stress augments insulin resistance and prothrombotic state: Role of visceral adipose‐derived monocyte chemoattractant protein‐1. Diabetes 61: 1552‐1561, 2012.
 183.Vaidya A, Underwood PA, Annes JP, Sun B, Wiliams GH, Forman JP, Williams JS. The influence of sodium‐ and calcium‐regulating hormone interventions on adipocytokines in obesity and diabetes. Metabolism 62: 539‐547, 2013.
 184.van den Craen B, Declerck PJ, Gils A. The biochemistry, physiology and pathological roles of PAI‐1 and the requirements for PAI‐1 inhibition in vivo. Thromb Res 130: 576‐585, 2012.
 185.van den Borst B, Schols AM, de Theije C, Boots AW, Köhler SE, Goossens GH, Gosker HR. Characterization of the inflammatory and metabolic profile of adipose tissue in a mouse model of chronic hypoxia. J Appl Physiol 114: 1619‐1628, 2013.
 186.Vaughan DE. Angintensin and vascular fibrinolytic balance. Am J Hypertens 15: 3S‐8S, 2002.
 187.Verrijken A, Francque S, Mertens I, Prawitt J, Caron S, Hubens G, Van Marck E, Staels B, Michielsen P, Van Gaal L. Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology 59: 121‐129, 2014.
 188.Willeit J, Kiechl S. Biology of arterial atheroma. Cerebrovasc Dis 10: 1‐8, 2000.
 189.Winkler UH, Altkemper R, Kwee B, Helmond FA, Coelingh Bennink HJ. Effects of tibolone and continuous combined hormone replacement therapy on parameters in the clotting cascade: A multucenter, double‐blind, randomized study. Fertil Steril 74: 10‐19, 2000.
 190.Wolfs MG, Gruben N, Rensen SS, Verdam FJ, Greve JW, Driessen A, Wijmenga C, Buurman WA, Franke L, Scheja L, Koonen DP, Shiri‐Sverdlov R, van Haeften TW, Hofker MH, Fu J. Determining the association between adipokine expression in multiple tissues and phenotypic features of non‐alcoholic fatty liver disease in obesity. Nutr Diabetes 5: e146, 2015.
 191.Xu AM, Vanhoutte PM. Adiponectin and adipocyte fatty acid binding protein in the pathogenesis of cardiovascular disease. Am J Physiol Heart Circ Physiol 302: H1231‐H1240, 2012.
 192.Yamamoto K, Kojima T, Takeshita K, Matsushita T, Takamatsu J. Pitavastatin attenuates the upregulation of tissue factor in restraint‐stressed mice. Thromb Res 120: 143‐144, 2007.
 193.Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin‐treated mice correlates with decreases in the expression of urokinase‐type but not tissue‐type plasminogen activator. J Clin Invest 97: 2440‐2451, 1997.
 194.Yamamoto K, Takeshita K, Kojima T, Takamatsu J, Saito H. Aging and plasminogen activator inhibitor‐1 (PAI‐1) regulation: Implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res 66: 276‐285, 2005.
 195.Yamamoto K, Takeshita K, Shimokawa T, Yi H, Isobe K, Loskutoff DJ, Saito H. Plasminogen activator inhibitor‐1 is a major stress‐regulated gene: Implications for stress‐induced thrombosis in aged individuals. Proc Natl Acad Sci USA 99: 890‐895, 2002.
 196.Yan L, Graef GL, Claycombe KJ, Johnson LK. Effects of voluntary running and soy supplementation on diet‐induced metabolic disturbance and inflammation in mice. J Agric Food Chem 61: 9373‐9379, 2013.
 197.Yan L, DeMars LC. Effects of a high‐fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor‐1 deficient and wild‐type mice. PLoS One 9: e110869, 2014.
 198.Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K. Brown adipose tissue, whole‐body energy expenditure, and thermogenesis in healthy adult men. Obesity 19: 13‐16, 2011.
 199.Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signaling from perivascular fat: A mechanism linking insulin resistance to vascular disease. Lancet 365: 1817‐1820, 2005.
 200.Zagotta I, Dimova EY, Funcke JB, Wabitsch M, Kietzmann T, Fischer‐Posovszky P. Resveratrol suppresses PAI‐1 gene expression in a human in vitro model of inflamed adipose tissue. Oxid Med Cell Longev 2013: 793525, 2013.
 201.Zhang ZF, Li Q, Liang J, Dai XQ, Ding Y, Wang JB, Li Y. Epigallocatechin‐3‐O‐gallate (EGCG) protects the insulin sensitivity in rat L6 muscle cells exposed to dexamethasone condition. Phytomedicine 17: 14‐18, 2010.
 202.Zhang Y, Zitman JL, Hou J, Fennoy H, Guo K, Feinberg J, Leibel RL. Fat cell size and adipokine expression in relation to gender, depot, and metabolic risk factors in morbidly obese adolescents. Obesity 22: 691‐697, 2014.

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Article Title: Adipose Tissue‐Derived Plasminogen Activator Inhibitor‐1 Function and Regulation
 

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Hiroshi Kaji. Adipose Tissue‐Derived Plasminogen Activator Inhibitor‐1 Function and Regulation. Compr Physiol 2016, 6: 1873-1896. doi: 10.1002/cphy.c160004