气候变化领域集成服务门户(CCPortal): Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension

CCPortal

DOI	10.1073/pnas.2023130118
	Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension
	Daneva Z.; Marziano C.; Ottolini M.; Chen Y.-L.; Baker T.M.; Kuppusamy M.; Zhang A.; Ta H.Q.; Reagan C.E.; Mihalek A.D.; Kasetti R.B.; Shen Y.; Isakson B.E.; Minshall R.D.; Zode G.S.; Goncharova E.A.; Laubach V.E.; Sonkusare S.K.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and lung injury. However, in pulmonary hypertension (PH), small pulmonary arteries are the focus of the pathology, and endothelial TRPV4 channels in this crucial anatomy remain unexplored in PH. Here, we provide evidence that TRPV4 channels in endothelial cell caveolae maintain a low pulmonary arterial pressure under normal conditions. Moreover, the activity of caveolar TRPV4 channels is impaired in pulmonary arteries from mouse models of PH and PH patients. In PH, up-regulation of iNOS and NOX1 enzymes at endothelial cell caveolae results in the formation of the oxidant molecule peroxynitrite. Peroxynitrite, in turn, targets the structural protein caveolin-1 to reduce the activity of TRPV4 channels. These results suggest that endothelial caveolin-1–TRPV4 channel signaling lowers pulmonary arterial pressure, and impairment of endothelial caveolin-1–TRPV4 channel signaling contributes to elevated pulmonary arterial pressure in PH. Thus, inhibiting NOX1 or iNOS activity, or lowering endothelial peroxynitrite levels, may represent strategies for restoring vasodilation and pulmonary arterial pressure in PH. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Caveolin; Endothelium; Peroxynitrite; Pulmonary hypertension; TRP channel
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179778
作者单位	Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, United States; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, United States; Department of Surgery, University of Virginia, Charlottesville, VA 22908, United States; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, United States; Department of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA 22908, United States; Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, United States; North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, United States; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, United States; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United...
推荐引用方式 GB/T 7714	Daneva Z.,Marziano C.,Ottolini M.,et al. Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension[J],2021,118(17).
APA	Daneva Z..,Marziano C..,Ottolini M..,Chen Y.-L..,Baker T.M..,...&Sonkusare S.K..(2021).Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Daneva Z.,et al."Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).