{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T21:10:51Z","timestamp":1771708251310,"version":"3.50.1"},"reference-count":50,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:p>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<jats:sup>Mut<\/jats:sup>) after they were fed a high-fat diet (HFD) for 16 wk. Kit<jats:sup>Mut<\/jats:sup>mice demonstrated substantially greater atherosclerosis compared with control (Kit<jats:sup>WT<\/jats:sup>) littermates ( P &lt; 0.01). Transplantation of c-Kit-positive bone marrow cells into Kit<jats:sup>Mut<\/jats:sup>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 &lt; 0.05). Markers of the \u201ccontractile\u201d SMC phenotype (calponin, SM22\u03b1) were downregulated with pharmacological and genetic c-Kit inhibition ( P &lt; 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<jats:sup>Mut<\/jats:sup>SMCs resulted in increased spindle-shaped morphology, reduced proliferation, and elevated levels of contractile markers, all indicators of their restored contractile phenotype ( P &lt; 0.05).<\/jats:p><jats:p>NEW &amp; NOTEWORTHY This study describes the novel vasculoprotective role of c-Kit against atherosclerosis and its function in the preservation of the SMC contractile phenotype.<\/jats:p>","DOI":"10.1152\/ajpheart.00062.2019","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T15:29:28Z","timestamp":1566574168000},"page":"H867-H876","source":"Crossref","is-referenced-by-count":10,"title":["c-Kit suppresses atherosclerosis in hyperlipidemic mice"],"prefix":"10.1152","volume":"317","author":[{"given":"Lei","family":"Song","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Miami, 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