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Lung Pericytes in Pulmonary Vascular Physiology and Pathophysiology

Ke Yuan, Stuti Agarwal, Ananya Chakraborty, David F. Condon, Hiral Patel, Serena Zhang, Flora Huang, Salvador A. Mello, Obadiah I. Kirk, Rocio Vasquez, Vinicio A. de Jesus Perez

10.1002/cphy.c200027

Source: Volume 11, Issue 3, July 2021

Published online: June 2021

Full Article on Wiley Online Library



Abstract

Pericytes are mesenchymal‐derived mural cells localized within the basement membrane of pulmonary and systemic capillaries. Besides structural support, pericytes control vascular tone, produce extracellular matrix components, and cytokines responsible for promoting vascular homeostasis and angiogenesis. However, pericytes can also contribute to vascular pathology through the production of pro‐inflammatory and pro‐fibrotic cytokines, differentiation into myofibroblast‐like cells, destruction of the extracellular matrix, and dissociation from the vessel wall. In the lung, pericytes are responsible for maintaining the integrity of the alveolar‐capillary membrane and coordinating vascular repair in response to injury. Loss of pericyte communication with alveolar capillaries and a switch to a pro‐inflammatory/pro‐fibrotic phenotype are common features of lung disorders associated with vascular remodeling, inflammation, and fibrosis. In this article, we will address how to differentiate pericytes from other cells, discuss the molecular mechanisms that regulate the interactions of pericytes and endothelial cells in the pulmonary circulation, and the experimental tools currently used to study pericyte biology both in vivo and in vitro. We will also discuss evidence that links pericytes to the pathogenesis of clinically relevant lung disorders such as pulmonary hypertension, idiopathic lung fibrosis, sepsis, and SARS‐COVID. Future studies dissecting the complex interactions of pericytes with other pulmonary cell populations will likely reveal critical insights into the origin of pulmonary diseases and offer opportunities to develop novel therapeutics to treat patients afflicted with these devastating disorders. © 2021 American Physiological Society. Compr Physiol 11:2227‐2247, 2021.

Figure 1. Figure 1. Distribution of pericytes across the length of the capillary wall. Note that the morphology of the pericyte can be variable depending on whether the pericyte is located close to the precapillary arteriole, the capillary body, or the postcapillary venule. Reused, with permission, from Hartmann DA, et al., 2015 68, Society of Photo‐Optical Instrumentation Engineers (SPIE). Licensed under CC BY 4.0.
Figure 2. Figure 2. Electron microscopy images of the human lung illustrate the intimate association between pericytes and endothelial cells in human lung capillaries. The pericytes are located within the basement membrane and extend long thin processes that establish contacts with the adjacent endothelial cell. Right panel is a higher magnification image of the area within the square. PP, pericyte processes; B, basement membrane; F, cytoplasmic filaments; E, endothelium; P, pericyte; A, alveolus.
Figure 3. Figure 3. Signaling pathways that regulate crosstalk between endothelial cells and pericytes in the vasculature. These events are critical for the establishment of functional vessels and disruption of one or more pathways can result in vascular dysfunction and inappropriate angiogenesis.


Figure 1. Distribution of pericytes across the length of the capillary wall. Note that the morphology of the pericyte can be variable depending on whether the pericyte is located close to the precapillary arteriole, the capillary body, or the postcapillary venule. Reused, with permission, from Hartmann DA, et al., 2015 68, Society of Photo‐Optical Instrumentation Engineers (SPIE). Licensed under CC BY 4.0.


Figure 2. Electron microscopy images of the human lung illustrate the intimate association between pericytes and endothelial cells in human lung capillaries. The pericytes are located within the basement membrane and extend long thin processes that establish contacts with the adjacent endothelial cell. Right panel is a higher magnification image of the area within the square. PP, pericyte processes; B, basement membrane; F, cytoplasmic filaments; E, endothelium; P, pericyte; A, alveolus.


Figure 3. Signaling pathways that regulate crosstalk between endothelial cells and pericytes in the vasculature. These events are critical for the establishment of functional vessels and disruption of one or more pathways can result in vascular dysfunction and inappropriate angiogenesis.
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Article Title: Lung Pericytes in Pulmonary Vascular Physiology and Pathophysiology
 

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Ke Yuan, Stuti Agarwal, Ananya Chakraborty, David F. Condon, Hiral Patel, Serena Zhang, Flora Huang, Salvador A. Mello, Obadiah I. Kirk, Rocio Vasquez, Vinicio A. de Jesus Perez. Lung Pericytes in Pulmonary Vascular Physiology and Pathophysiology. Compr Physiol 2021, 11: 2227-2247. doi: 10.1002/cphy.c200027