Abstract
肺动脉高压(PAH)是一个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.
Abstract
Dysfunctional endothelial cells play an important role in initiating and progressing PAH by impacting on multi-aspects of vascular remodelling and vasoconstriction. EC-targeted therapy may be effective in inhibiting vascular remodelling to treat PAH.https://bit.ly/3nXPvMB
Footnotes
Author contributions: C.E. Evans wrote the manuscript; N.D. Cober, Z. Dai and D.J. Stewart edited the manuscript; and Y-Y. Zhao revised and finalised the manuscript. All authors approved the final version.
Conflict of interest: N.D. Cober reports grants from Canadian Institute of Health Research and Canadian Vascular Network, during the conduct of the study.
Conflict of interest: Z. Dai reports grants from National Institutes of Health, American Heart Association and American Thoracic Society, during the conduct of the study.
Conflict of interest: D.J. Stewart reports other (founding member, equity stake) from Northern Therapeutics, outside the submitted work.
Conflict of interest: 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.
Conflict of interest: C.E. Evans reports grants (Career Development Award, 19CDA34500000) from American Heart Association, during the conduct of the study.
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 theCrossref Funder Registry.
- ReceivedOctober 27, 2020.
- AcceptedJanuary 13, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contactpermissions{at}ersnet.org