Abstract
Pulmonary arterial hypertension (PAH) is a devastating disease that involves pulmonary vasoconstriction, small vessel obliteration, large vessel thickening and obstruction, and development of plexiform lesions. PAH vasculopathy leads to progressive increases in pulmonary vascular resistance, right heart failure, and ultimately, premature death. Besides other cell types that are known to be involved in PAH pathogenesis (e.g.smooth muscle cells, fibroblasts, and leukocytes), recent studies demonstrate a crucial role of endothelial cells (ECs) in the initiation and progression of PAH. The EC-specific role in PAH is multi-faceted and impacts upon numerous pathophysiological processes including vasoconstriction, inflammation, coagulation, metabolism, and oxidative/nitrative stress, as well as cell viability, growth, and differentiation. In this review, we describe how EC dysfunction and cell signalling regulate the pathogenesis of PAH. We also highlight areas of research that warrant attention in future studies, and discuss potential molecular signalling pathways in ECs that could be targeted therapeutically in the prevention and treatment of PAH.
Footnotes
This manuscript has recently been accepted for publication in theEuropean Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of theERJonline. Please open or download the PDF to view this article.
Conflict of interest: Dr. Evans reports grants from American Heart Association, during the conduct of the study;.
Conflict of interest: N. Cober reports grants from Canadian Institute of Health Research, grants from Canadian Vascular Network, during the conduct of the study.
Conflict of interest: Dr. Dai reports grants from NIH, grants from AHA, grants from ATS, during the conduct of the study.
Conflict of interest: Dr. Stewart reports other from Northern Therapeutics, outside the submitted work.
Conflict of interest: Dr. Zhao reports grants from NIH/NHLBI, during the conduct of the study;.
- ReceivedOctober 27, 2020.
- AcceptedJanuary 13, 2021.
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