Myocardin regulates vascular smooth muscle cell inflammatory activation and disease.
Myocardin regulates vascular smooth muscle cell inflammatory activation and disease.
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DOI：
10.1161/atvbaha.114.305218
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Sinha S
中科院分区：
文献类型：
--
作者：
Ackers-Johnson M;Talasila A;Sage AP;Long X;Bot I;Morrell NW;Bennett MR;Miano JM;Sinha S
Atherosclerosis, the cause of 50% of deaths in westernised societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local pro-inflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable therapeutic importance to identify mechanisms that regulate the VSMC inflammatory response. We report that myocardin, a powerful myogenic transcriptional coactivator, negatively regulates VSMC inflammatory activation and vascular disease. Myocardin levels are reduced during atherosclerosis, in association with phenotypic switching of smooth muscle cells. Myocardin deficiency accelerates atherogenesis in hypercholesterolemic ApoE−/− mice. Conversely, increased myocardin expression potently abrogates the induction of an array of inflammatory cytokines, chemokines and adhesion molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake, macrophage interaction, chemotaxis and macrophage-endothelial tethering in vitro, and attenuates monocyte accumulation within developing lesions in vivo. These results demonstrate that endogenous levels of myocardin are a critical regulator of vessel inflammation. We propose myocardin as a guardian of the contractile, non-inflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease.
