Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels

Abstract The maladaptive remodeling of vessel walls with neointima formation is a common feature of proliferative vascular diseases. It has been proposed that neointima formation is caused by the dedifferentiation of mature smooth muscle cells (SMCs). Recent evidence suggests that adventitial cells...

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Autores principales:	Kenichi Kimura, Karina Ramirez, Tram Anh Vu Nguyen, Yoshito Yamashiro, Aiko Sada, Hiromi Yanagisawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/89bd0723c4584fb39e56cd1068a37403
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spelling	oai:doaj.org-article:89bd0723c4584fb39e56cd1068a374032021-12-02T18:27:47ZContribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels10.1038/s41598-021-88126-62045-2322https://doaj.org/article/89bd0723c4584fb39e56cd1068a374032021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88126-6https://doaj.org/toc/2045-2322Abstract The maladaptive remodeling of vessel walls with neointima formation is a common feature of proliferative vascular diseases. It has been proposed that neointima formation is caused by the dedifferentiation of mature smooth muscle cells (SMCs). Recent evidence suggests that adventitial cells also participate in neointima formation; however, their cellular dynamics are not fully understood. In this study, we utilized a lineage tracing model of platelet-derived growth factor receptor alpha (PDGFRa) cells and examined cellular behavior during homeostasis and injury response. PDGFRa marked adventitial cells that were largely positive for Sca1 and a portion of medial SMCs, and both cell types were maintained for 2 years. Upon carotid artery ligation, PDGFRa-positive (+) cells were slowly recruited to the neointima and exhibited an immature SMC phenotype. In contrast, in a more severe wire denudation injury, PDGFRa+ cells were recruited to the neointima within 14 days and fully differentiated into SMCs. Under pressure overload induced by transverse aortic constriction, PDGFRa+ cells developed marked adventitial fibrosis. Taken together, our observations suggest that PDGFRa+ cells serve as a reservoir of adventitial cells and a subset of medial SMCs and underscore their context-dependent response to vascular injuries.Kenichi KimuraKarina RamirezTram Anh Vu NguyenYoshito YamashiroAiko SadaHiromi YanagisawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenichi Kimura Karina Ramirez Tram Anh Vu Nguyen Yoshito Yamashiro Aiko Sada Hiromi Yanagisawa Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels
description	Abstract The maladaptive remodeling of vessel walls with neointima formation is a common feature of proliferative vascular diseases. It has been proposed that neointima formation is caused by the dedifferentiation of mature smooth muscle cells (SMCs). Recent evidence suggests that adventitial cells also participate in neointima formation; however, their cellular dynamics are not fully understood. In this study, we utilized a lineage tracing model of platelet-derived growth factor receptor alpha (PDGFRa) cells and examined cellular behavior during homeostasis and injury response. PDGFRa marked adventitial cells that were largely positive for Sca1 and a portion of medial SMCs, and both cell types were maintained for 2 years. Upon carotid artery ligation, PDGFRa-positive (+) cells were slowly recruited to the neointima and exhibited an immature SMC phenotype. In contrast, in a more severe wire denudation injury, PDGFRa+ cells were recruited to the neointima within 14 days and fully differentiated into SMCs. Under pressure overload induced by transverse aortic constriction, PDGFRa+ cells developed marked adventitial fibrosis. Taken together, our observations suggest that PDGFRa+ cells serve as a reservoir of adventitial cells and a subset of medial SMCs and underscore their context-dependent response to vascular injuries.
format	article
author	Kenichi Kimura Karina Ramirez Tram Anh Vu Nguyen Yoshito Yamashiro Aiko Sada Hiromi Yanagisawa
author_facet	Kenichi Kimura Karina Ramirez Tram Anh Vu Nguyen Yoshito Yamashiro Aiko Sada Hiromi Yanagisawa
author_sort	Kenichi Kimura
title	Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels
title_short	Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels
title_full	Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels
title_fullStr	Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels
title_full_unstemmed	Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels
title_sort	contribution of pdgfrα-positive cells in maintenance and injury responses in mouse large vessels
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/89bd0723c4584fb39e56cd1068a37403
work_keys_str_mv	AT kenichikimura contributionofpdgfrapositivecellsinmaintenanceandinjuryresponsesinmouselargevessels AT karinaramirez contributionofpdgfrapositivecellsinmaintenanceandinjuryresponsesinmouselargevessels AT tramanhvunguyen contributionofpdgfrapositivecellsinmaintenanceandinjuryresponsesinmouselargevessels AT yoshitoyamashiro contributionofpdgfrapositivecellsinmaintenanceandinjuryresponsesinmouselargevessels AT aikosada contributionofpdgfrapositivecellsinmaintenanceandinjuryresponsesinmouselargevessels AT hiromiyanagisawa contributionofpdgfrapositivecellsinmaintenanceandinjuryresponsesinmouselargevessels
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Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels

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