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• W2969550733 abstract "Atherosclerosis is the most common underlying cause of cardiovascular morbidity and mortality worldwide. c-Kit (CD117) is a member of the receptor tyrosine kinase family, which regulates differentiation, proliferation, and survival of multiple cell types. Recent studies have shown that c-Kit and its ligand stem cell factor (SCF) are present in arterial endothelial cells and smooth muscle cells (SMCs). The role of c-Kit in cardiovascular disease remains unclear. The aim of the current study is to determine the role of c-Kit in atherogenesis. For this purpose, atherosclerotic plaques were quantified in c-Kit-deficient mice (Kit Mut ) after they were fed a high-fat diet (HFD) for 16 wk. Kit Mut mice demonstrated substantially greater atherosclerosis compared with control (Kit WT ) littermates ( P < 0.01). Transplantation of c-Kit-positive bone marrow cells into Kit Mut mice failed to rescue the atherogenic phenotype, an indication that increased atherosclerosis was associated with reduced arterial c-Kit. To investigate the mechanism, SMC organization and morphology were analyzed in the aorta by histopathology and electron microscopy. SMCs were more abundant, disorganized, and vacuolated in aortas of c-Kit mutant mice compared with controls ( P < 0.05). Markers of the “contractile” SMC phenotype (calponin, SM22α) were downregulated with pharmacological and genetic c-Kit inhibition ( P < 0.05). The absence of c-Kit increased lipid accumulation and significantly reduced the expression of the ATP-binding cassette transporter G1 (ABCG1) necessary for lipid efflux in SMCs. Reconstitution of c-Kit in cultured Kit Mut SMCs resulted in increased spindle-shaped morphology, reduced proliferation, and elevated levels of contractile markers, all indicators of their restored contractile phenotype ( P < 0.05). NEW & NOTEWORTHY This study describes the novel vasculoprotective role of c-Kit against atherosclerosis and its function in the preservation of the SMC contractile phenotype." @default.
• W2969550733 created "2019-08-29" @default.
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• W2969550733 date "2019-10-01" @default.
• W2969550733 modified "2023-10-11" @default.
• W2969550733 title "c-Kit suppresses atherosclerosis in hyperlipidemic mice" @default.
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• W2969550733 doi "https://doi.org/10.1152/ajpheart.00062.2019" @default.
• W2969550733 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6843012" @default.
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