Cellular communication network factor 2 regulates smooth muscle cell transdifferentiation and lipid accumulation in atherosclerosis.

Autor:	Xu Q; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA.; Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China., Sun J; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA., Holden CM; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA., Neto HCF; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA., Wang T; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA.; The Hospital Affiliated to Medical School of Yangzhou University (Taizhou People's Hospital), Yangzhou University Medical College, Jiangsu, China., Zhang C; Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China., Fu Z; Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China., Joseph G; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA., Shi R; Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China., Wang J; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA., Leask A; College of Dentistry, University of Saskatchewan, 105 Wiggins Road, Saskatoon, SK, Canada., Taylor WR; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA., Lin Z; Cardiology Division, Department of Medicine, Emory University School of Medicine, 1750 Haygood Drive, Atlanta, GA 30322, USA.
Jazyk:	angličtina
Zdroj:	Cardiovascular research [Cardiovasc Res] 2024 Dec 31; Vol. 120 (17), pp. 2191-2207.
DOI:	10.1093/cvr/cvae215
Abstrakt:	Aims: Accruing evidence illustrates an emerging paradigm of dynamic vascular smooth muscle cell (SMC) transdifferentiation during atherosclerosis progression. However, the molecular regulators that govern SMC phenotype diversification remain poorly defined. This study aims to elucidate the functional role and underlying mechanisms of cellular communication network factor 2 (CCN2), a matricellular protein, in regulating SMC plasticity in the context of atherosclerosis. Methods and Results: In both human and murine atherosclerosis, an up-regulation of CCN2 is observed in transdifferentiated SMCs. Using an inducible murine SMC CCN2 deletion model, we demonstrate that SMC-specific CCN2 knockout mice are hypersusceptible to atherosclerosis development as evidenced by a profound increase in lipid-rich plaques along the entire aorta. Single-cell RNA sequencing studies reveal that SMC deficiency of CCN2 positively regulates machinery involved in endoplasmic reticulum stress, endocytosis, and lipid accumulation in transdifferentiated macrophage-like SMCs during the progression of atherosclerosis, findings recapitulated in CCN2-deficient human aortic SMCs. Conclusion: Our studies illuminate an unanticipated protective role of SMC-CCN2 against atherosclerosis. Disruption of vascular wall homeostasis resulting from vascular SMC CCN2 deficiency predisposes mice to atherosclerosis development and progression. Competing Interests: Conflict of interest: none declared. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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