Nitric Oxide-Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Marziano, Corina | - |
dc.contributor.author | Hong, Kwangseok | - |
dc.contributor.author | Cope, Eric L. | - |
dc.contributor.author | Kotlikoff, Michael I. | - |
dc.contributor.author | Isakson, Brant E. | - |
dc.contributor.author | Sonkusare, Swapnil K. | - |
dc.date.accessioned | 2021-06-18T08:41:23Z | - |
dc.date.available | 2021-06-18T08:41:23Z | - |
dc.date.issued | 2017-12 | - |
dc.identifier.issn | 2047-9980 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/45461 | - |
dc.description.abstract | Background-Recent studies demonstrate that spatially restricted, local Ca2+ signals are key regulators of endothelium-dependent vasodilation in systemic circulation. There are drastic functional differences between pulmonary arteries (PAs) and systemic arteries, but the local Ca2+ signals that control endothelium-dependent vasodilation of PAs are not known. Localized, unitary Ca2+ influx events through transient receptor potential vanilloid 4 (TRPV4) channels, termed TRPV4 sparklets, regulate endothelium-dependent vasodilation in resistance-sized mesenteric arteries via activation of Ca2+-dependent K+ channels. The objective of this study was to determine the unique functional roles, signaling targets, and endogenous regulators of TRPV4 sparklets in resistance-sized PAs. Methods and Results-Using confocal imaging, custom image analysis, and pressure myography in fourth-order PAs in conjunction with knockout mouse models, we report a novel Ca2+ signaling mechanism that regulates endothelium-dependent vasodilation in resistance-sized PAs. TRPV4 sparklets exhibit distinct spatial localization in PAs when compared with mesenteric arteries, and preferentially activate endothelial nitric oxide synthase (eNOS). Nitric oxide released by TRPV4-endothelial nitric oxide synthase signaling not only promotes vasodilation, but also initiates a guanylyl cyclase-protein kinase G-dependent negative feedback loop that inhibits cooperative openings of TRPV4 channels, thus limiting sparklet activity. Moreover, we discovered that adenosine triphosphate dilates PAs through a P2 purinergic receptor-dependent activation of TRPV4 sparklets. Conclusions-Our results reveal a spatially distinct TRPV4-endothelial nitric oxide synthase signaling mechanism and its novel endogenous regulators in resistance-sized PAs. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | WILEY | - |
dc.title | Nitric Oxide-Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries | - |
dc.type | Article | - |
dc.identifier.doi | 10.1161/JAHA.117.007157 | - |
dc.identifier.bibliographicCitation | JOURNAL OF THE AMERICAN HEART ASSOCIATION, v.6, no.12 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.wosid | 000418951100044 | - |
dc.identifier.scopusid | 2-s2.0-85053871462 | - |
dc.citation.number | 12 | - |
dc.citation.title | JOURNAL OF THE AMERICAN HEART ASSOCIATION | - |
dc.citation.volume | 6 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | calcium channel | - |
dc.subject.keywordAuthor | calcium signaling | - |
dc.subject.keywordAuthor | endothelial nitric oxide synthase | - |
dc.subject.keywordAuthor | endothelium | - |
dc.subject.keywordAuthor | microcirculation | - |
dc.subject.keywordAuthor | pulmonary artery | - |
dc.subject.keywordAuthor | signaling pathways | - |
dc.subject.keywordAuthor | transient receptor potential vanilloid 4 channel | - |
dc.subject.keywordAuthor | vascular endothelial function | - |
dc.subject.keywordPlus | SOLUBLE GUANYLATE-CYCLASE | - |
dc.subject.keywordPlus | CA2+ CHANNELS | - |
dc.subject.keywordPlus | ATP RELEASE | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | SYNTHASE | - |
dc.subject.keywordPlus | LUNG | - |
dc.subject.keywordPlus | HYPOXIA | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.relation.journalResearchArea | Cardiovascular System & Cardiology | - |
dc.relation.journalWebOfScienceCategory | Cardiac & Cardiovascular Systems | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.