4.4 Article

Lung Pericytes in Pulmonary Vascular Physiology and Pathophysiology

Journal

COMPREHENSIVE PHYSIOLOGY
Volume 11, Issue 3, Pages 2227-2247

Publisher

WILEY
DOI: 10.1002/cphy.c200027

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Categories

Funding

  1. NIH [R01 HL134776, R01 HL139664]
  2. American Heart Association Scientist Development Grant [15SDG25710448]
  3. Parker B. Francis Fellowship
  4. Pulmonary Hypertension Association Aldrighetti Research Award

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Pericytes are mural cells derived from mesenchyme located within the basement membrane of pulmonary and systemic capillaries, playing important roles in vascular homeostasis, angiogenesis, and pathology. Dysregulation of pericyte communication and phenotype switching are common features of lung disorders associated with vascular remodeling, inflammation, and fibrosis, indicating their potential involvement in the pathogenesis of these diseases.
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 home-ostasis 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. (C) 2021 American Physiological Society.

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