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 have demonstrated that endothelial cells (ECs) have a crucial role in the initiation and progression of PAH. The EC-specific role in PAH is multi-faceted and affects 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.
| Original language | English (US) |
|---|---|
| Article number | 2003957 |
| Journal | European Respiratory Journal |
| Volume | 58 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2021 |
Funding
Support statement: This work was supported in part by NIH grants R01HL123957, R01HL133951, R01HL140409 and R01HL148810 to Y-Y. Zhao and by an American Heart Association Career Development Award (19CDA34500000) to C.E. Evans. Funding information for this article has been deposited with the Crossref Funder Registry. Conflict of interest: N.D. Cober reports grants from Canadian Institute of Health Research and Canadian Vascular Network, during the conduct of the study. Z. Dai reports grants from National Institutes of Health, American Heart Association and American Thoracic Society, during the conduct of the study. D.J. Stewart reports other (founding member, equity stake) from Northern Therapeutics, outside the submitted work. Y-Y. Zhao reports grants from National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL123957, R01HL133951, R01HL140409 and R01HL148810), during the conduct of the study. C.E. Evans reports grants (Career Development Award, 19CDA34500000) from American Heart Association, during the conduct of the study.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
