C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their Proliferation in Aortic Explants and Atherosclerotic Lesions
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zhou, Alex-Xianghua | - |
dc.contributor.author | Wang, Xiaobo | - |
dc.contributor.author | Lin, Chyuan Sheng | - |
dc.contributor.author | Han, Jaeseok | - |
dc.contributor.author | Yong, Jing | - |
dc.contributor.author | Nadolski, Marissa J. | - |
dc.contributor.author | Boren, Jan | - |
dc.contributor.author | Kaufman, Randal J. | - |
dc.contributor.author | Tabas, Ira | - |
dc.date.accessioned | 2021-08-11T20:24:58Z | - |
dc.date.available | 2021-08-11T20:24:58Z | - |
dc.date.issued | 2015-05-22 | - |
dc.identifier.issn | 0009-7330 | - |
dc.identifier.issn | 1524-4571 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10641 | - |
dc.description.abstract | Rationale: Myeloid-derived C/EBP-homologous protein (CHOP), an effector of the endoplasmic reticulum stress-induced unfolded protein response, promotes macrophage apoptosis in advanced atherosclerosis, but the role of CHOP in vascular smooth muscle cells (VSMCs) in atherosclerosis is not known. Objective: To investigate the role of CHOP in SM22 alpha(+) VSMCs in atherosclerosis. Methods and Results: Chop(fl/fl) mice were generated and crossed into the Apoe(-/-) and SM22 alpha-CreKI(+) backgrounds. SM22 alpha-CreKI causes deletion of floxed genes in adult SMCs. After 12 weeks of Western-type diet feeding, the content of alpha-actin-positive cells in aortic root lesions was decreased in Chop(fl/fl)SM22 alpha-CreKI(+) Apoe(-/-) versus control Chop(fl/fl)Apoe(-/-) mice, and aortic explant-derived VSMCs from the VSMC-CHOP-deficient mice displayed reduced proliferation. Kruppel-like factor 4 (KLF4), a key suppressor of VSMC proliferation, was increased in lesions and aortic VSMCs from Chop(fl/fl)SM22 alpha-CreKI(+) Apoe(-/-) mice, and silencing Klf4 in CHOP-deficient VSMCs restored proliferation. CHOP deficiency in aortic VSMCs increased KLF4 through 2 mechanisms mediated by the endoplasmic reticulum stress effector activating transcription factor 4: transcriptional induction of Klf4 mRNA and decreased proteasomal degradation of KLF4 protein. Conclusions: These findings in SM22 alpha-CHOP-deficient mice imply that CHOP expression in SM22 alpha(+) VSMCs promotes cell proliferation by downregulating KLF4. The mechanisms involve newly discovered roles of CHOP in the transcriptional and post-translational regulation of KLF4. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Lippincott Williams & Wilkins Ltd. | - |
dc.title | C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their Proliferation in Aortic Explants and Atherosclerotic Lesions | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1161/CIRCRESAHA.116.305602 | - |
dc.identifier.scopusid | 2-s2.0-84942777039 | - |
dc.identifier.wosid | 000354861500006 | - |
dc.identifier.bibliographicCitation | Circulation Research, v.116, no.11, pp 1736 - + | - |
dc.citation.title | Circulation Research | - |
dc.citation.volume | 116 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 1736 | - |
dc.citation.endPage | + | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cardiovascular System & Cardiology | - |
dc.relation.journalResearchArea | Hematology | - |
dc.relation.journalWebOfScienceCategory | Cardiac & Cardiovascular Systems | - |
dc.relation.journalWebOfScienceCategory | Hematology | - |
dc.relation.journalWebOfScienceCategory | Peripheral Vascular Disease | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | INITIATION | - |
dc.subject.keywordPlus | PLAQUES | - |
dc.subject.keywordPlus | APOE | - |
dc.subject.keywordAuthor | activating transcription factor 4 | - |
dc.subject.keywordAuthor | atherosclerosis | - |
dc.subject.keywordAuthor | transcription factor CHOP | - |
dc.subject.keywordAuthor | unfolded protein response | - |
dc.subject.keywordAuthor | vascular smooth muscle cells | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(31538) 22, Soonchunhyang-ro, Asan-si, Chungcheongnam-do, Republic of Korea+82-41-530-1114
COPYRIGHT 2021 by SOONCHUNHYANG 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.