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Inflammatory Mechanisms in the Pathogenesis of Pulmonary Arterial Hypertension: Recent Advances

Valentina Mercurio, Alessandra Cuomo, Mario Naranjo, Paul M. Hassoun

10.1002/cphy.c200025

Source: Volume 11, Issue 2, April 2021

Published online: April 2021

Full Article on Wiley Online Library



Abstract

Inflammatory processes are increasingly recognized in the pathogenesis of the vascular remodeling that characterizes pulmonary arterial hypertension (PAH). Chronic inflammation may contribute to disease progression or serve as a biomarker of PAH severity. Furthermore, inflammatory pathways may represent possible therapeutic targets for novel PAH‐specific drugs beyond the currently approved therapies targeting the endothelin, nitric oxide/cyclic GMP, and prostacyclin biological pathways. The main focus of this article is to provide recent advances in the understanding of the role of inflammatory pathways in the pathogenesis of PAH from preclinical studies and current clinical data supporting chronic inflammation in PAH patients and to discuss emerging therapeutic implications. © 2021 American Physiological Society. Compr Physiol 11:1805‐1829, 2021.

Keywords: Inflammation; inflammatory mechanisms; inflammatory pathways; chemokines; cytokines; growth factors; inflammatory cells; pulmonary hypertension; pulmonary arterial hypertension; pulmonary vessels; pulmonary vascular remodeling

Figure 1. Figure 1. This figure illustrates the relationship between inflammation and pulmonary arterial hypertension (PAH). List of abbreviations: BMPR2, bone morphogenic protein receptor 2; CHD, congenital heart disease; HIV, human immunodeficiency virus; Sars‐CoV‐2, severe acute respiratory syndrome coronavirus 2; NK, natural killers; Th1, T helper 1 lymphocytes; Th2, T helper 2 lymphocytes; Th17 T helper 17 lymphocytes; T‐regs, regulatory T lymphocytes; tLT, tertiary lymphoid tissue; PA‐EC, pulmonary artery endothelial cell; MIF, macrophage migration inhibitory factor; IL‐6, interleukin‐6; ICAM, intercellular adhesion molecule; VCAM, vascular cell adhesion molecule; TLR4, toll‐like receptor‐4 TNF‐α, tumor necrosis factor‐ α; IL‐1β, interleukin‐1 β; TGF‐β, tumor growth factor‐β; PA‐SMC, pulmonary artery smooth muscle cell; MyD88, myeloid differentiation primary response 88; ObR, leptin receptor; STAT3, signal transducer and activator of transcription 3; NF‐κB, nuclear factor kappa‐light‐chain‐enhancer of activated B cells; FoxM1, forkhead box protein M1; CXCL12, stromal cell‐derived factor 1 also known as C‐X‐C motif chemokine 12; FGF2, fibroblast growth factor 2.
Figure 2. Figure 2. This figure illustrates the histological alterations in pulmonary arterial vessels in PAH. Panel A represents a normal pulmonary arterial vessel, characterized by the presence of three thin layers composed of the intima, the media, and the adventitia. Panel B represents a remodeled vessel.


Figure 1. This figure illustrates the relationship between inflammation and pulmonary arterial hypertension (PAH). List of abbreviations: BMPR2, bone morphogenic protein receptor 2; CHD, congenital heart disease; HIV, human immunodeficiency virus; Sars‐CoV‐2, severe acute respiratory syndrome coronavirus 2; NK, natural killers; Th1, T helper 1 lymphocytes; Th2, T helper 2 lymphocytes; Th17 T helper 17 lymphocytes; T‐regs, regulatory T lymphocytes; tLT, tertiary lymphoid tissue; PA‐EC, pulmonary artery endothelial cell; MIF, macrophage migration inhibitory factor; IL‐6, interleukin‐6; ICAM, intercellular adhesion molecule; VCAM, vascular cell adhesion molecule; TLR4, toll‐like receptor‐4 TNF‐α, tumor necrosis factor‐ α; IL‐1β, interleukin‐1 β; TGF‐β, tumor growth factor‐β; PA‐SMC, pulmonary artery smooth muscle cell; MyD88, myeloid differentiation primary response 88; ObR, leptin receptor; STAT3, signal transducer and activator of transcription 3; NF‐κB, nuclear factor kappa‐light‐chain‐enhancer of activated B cells; FoxM1, forkhead box protein M1; CXCL12, stromal cell‐derived factor 1 also known as C‐X‐C motif chemokine 12; FGF2, fibroblast growth factor 2.


Figure 2. This figure illustrates the histological alterations in pulmonary arterial vessels in PAH. Panel A represents a normal pulmonary arterial vessel, characterized by the presence of three thin layers composed of the intima, the media, and the adventitia. Panel B represents a remodeled vessel.
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Article Title: Inflammatory Mechanisms in the Pathogenesis of Pulmonary Arterial Hypertension: Recent Advances
 

How to Cite

Valentina Mercurio, Alessandra Cuomo, Mario Naranjo, Paul M. Hassoun. Inflammatory Mechanisms in the Pathogenesis of Pulmonary Arterial Hypertension: Recent Advances. Compr Physiol 2021, 11: 1805-1829. doi: 10.1002/cphy.c200025