Dedicator of cytokinesis 2, a novel regulator for smooth muscle phenotypic modulation and vascular remodeling

Circulation Research
Xia GuoShi-You Chen

Abstract

Vascular smooth muscle cell (SMC) phenotypic modulation and vascular remodeling contribute to the development of several vascular disorders such as restenosis after angioplasty, transplant vasculopathy, and atherosclerosis. The mechanisms underlying these processes, however, remain largely unknown. The objective of this study is to determine the role of dedicator of cytokinesis 2 (DOCK2) in SMC phenotypic modulation and vascular remodeling. Platelet-derived growth factor-BB induced DOCK2 expression while modulating SMC phenotype. DOCK2 deficiency diminishes platelet-derived growth factor-BB or serum-induced downregulation of SMC markers. Conversely, DOCK2 overexpression inhibits SMC marker expression in primary cultured SMC. Mechanistically, DOCK2 inhibits myocardin expression, blocks serum response factor nuclear location, attenuates myocardin binding to serum response factor, and thus attenuates myocardin-induced smooth muscle marker promoter activity. Moreover, DOCK2 and Kruppel-like factor 4 cooperatively inhibit myocardin-serum response factor interaction. In a rat carotid artery balloon-injury model, DOCK2 is induced in media layer SMC initially and neointima SMC subsequently after vascular injury. Knockdown of DOCK2 dram...Continue Reading

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Citations

Oct 2, 2015·Journal of Cellular Physiology·Ning Shi, Shi-You Chen
Aug 10, 2016·Journal of Cellular Physiology·Xia Guo, Shi-You Chen
Feb 1, 2018·Cardiovascular Research·Sima AllahverdianMarie-Luce Bochaton-Piallat
May 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Ning Shi, Shi-You Chen
Apr 28, 2019·Journal of Molecular Histology·Tingjuan NiHangyuan Guo
Jul 13, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Chen HuangYuelin Zhu
Jul 29, 2020·Journal of the American Heart Association·Lin-Juan DuSheng-Zhong Duan
Dec 4, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Ran RanShi-You Chen
Feb 7, 2021·Angiogenesis·Clare E Benson, Laura Southgate
May 1, 2021·Journal of Clinical Immunology·Katherine D'Astous-GauthierHugo Chapdelaine
Apr 24, 2019·Journal of Vascular Surgery·Chen HuangXiaobing Zheng
Sep 3, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Carmen YapVivian de Waard

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