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C/EBP-Homologous Pr...
C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their Proliferation in Aortic Explants and Atherosclerotic Lesions
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- Zhou, Alex-Xianghua (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Wang, X. B. (författare)
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Lin, C. S. (författare)
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Han, J. (författare)
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Yong, J. (författare)
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Nadolski, M. J. (författare)
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- Borén, Jan, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Kaufman, R. J. (författare)
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Tabas, I. (författare)
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(creator_code:org_t)
- Ovid Technologies (Wolters Kluwer Health), 2015
- 2015
- Engelska.
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Ingår i: Circulation Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7330 .- 1524-4571. ; 116:11
- Relaterad länk:
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https://www.ahajourn...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- activating transcription factor 4
- atherosclerosis
- transcription factor CHOP
- unfolded protein
- ENDOPLASMIC-RETICULUM STRESS
- GENE-EXPRESSION
- MECHANISMS
- APOPTOSIS
- PLAQUES
- MACROPHAGES
- PROGRESSION
- ACTIVATION
- INITIATION
- RESPONSES
- Cardiac & Cardiovascular Systems
- Hematology
- Peripheral Vascular
- Disease
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Zhou, Alex-Xiang ...
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Wang, X. B.
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Lin, C. S.
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Han, J.
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Yong, J.
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Nadolski, M. J.
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visa fler...
-
Borén, Jan, 1963
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Kaufman, R. J.
-
Tabas, I.
-
visa färre...
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Göteborgs universitet