| First Author | Song L | Year | 2019 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 317 |
| Issue | 4 | Pages | H867-H876 |
| PubMed ID | 31441677 | Mgi Jnum | J:288643 |
| Mgi Id | MGI:6363190 | Doi | 10.1152/ajpheart.00062.2019 |
| Citation | Song L, et al. (2019) c-Kit suppresses atherosclerosis in hyperlipidemic mice. Am J Physiol Heart Circ Physiol 317(4):H867-H876 |
| abstractText | 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, SM22alpha) 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. |
