Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Srivastava, Roshni | - |
dc.contributor.author | Zhang, Jiasheng | - |
dc.contributor.author | Go, Gwang-woong | - |
dc.contributor.author | Narayanan, Anand | - |
dc.contributor.author | Nottoli, Timothy P. | - |
dc.contributor.author | Mani, Arya | - |
dc.date.accessioned | 2022-07-15T20:39:58Z | - |
dc.date.available | 2022-07-15T20:39:58Z | - |
dc.date.created | 2021-05-13 | - |
dc.date.issued | 2015-10 | - |
dc.identifier.issn | 22111247 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/156123 | - |
dc.description.abstract | Mutations in Wnt-signaling coreceptor LRP6 have been linked to coronary artery disease (CAD) by unknown mechanisms. Here, we show that reduced LRP6 activity in LRP6(R611C) mice promotes loss of vascular smooth muscle cell (VSMC) differentiation, leading to aortic medial hyperplasia. Carotid injury augmented these effects and led to partial to total vascular obstruction. LRP6(R611C) mice on high-fat diet displayed dramatic obstructive CAD and exhibited an accelerated atherosclerotic burden on LDLR knockout background. Mechanistically, impaired LRP6 activity leads to enhanced non-canonical Wnt signaling, culminating in diminished TCF7L2 and increased Sp1-dependent activation of PDGF signaling. Wnt3a administration to LRP6(R611C) mice improved LRP6 activity, led to TCF7L2-dependent VSMC differentiation, and rescued post-carotid-injury neointima formation. These findings demonstrate the critical role of intact Wnt signaling in the vessel wall, establish a causal link between impaired LRP6/TCF7L2 activities and arterial disease, and identify Wnt signaling as a therapeutic target against CAD. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | CELL PRESS | - |
dc.title | Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Srivastava, Roshni | - |
dc.identifier.doi | 10.1016/j.celrep.2015.09.028 | - |
dc.identifier.scopusid | 2-s2.0-84945546762 | - |
dc.identifier.wosid | 000363780900011 | - |
dc.identifier.bibliographicCitation | CELL REPORTS, v.13, no.4, pp.746 - 759 | - |
dc.relation.isPartOf | CELL REPORTS | - |
dc.citation.title | CELL REPORTS | - |
dc.citation.volume | 13 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 746 | - |
dc.citation.endPage | 759 | - |
dc.type.rims | ART | - |
dc.type.docType | 정기학술지(Article(Perspective Article포함)) | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordAuthor | MACROPHAGE-LIKE CELLS | - |
dc.subject.keywordAuthor | NONCANONICAL WNT | - |
dc.subject.keywordAuthor | BETA-CATENIN | - |
dc.subject.keywordAuthor | LRP6 | - |
dc.subject.keywordAuthor | GENE | - |
dc.subject.keywordAuthor | TRANSCRIPTION | - |
dc.subject.keywordAuthor | ATHEROSCLEROSIS | - |
dc.subject.keywordAuthor | PHOSPHORYLATION | - |
dc.subject.keywordAuthor | EXPRESSION | - |
dc.subject.keywordAuthor | PHENOTYPE | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S2211124715010396?via%3Dihub | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
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.