Abstract 16456: Regulation of Vascular Smooth Muscle Phenotypic Switch and Suppression of Atherosclerosis by c-Kit/SCF Expression in Hyperlipidemic Mice

Introduction: This study provides our novel evidence that stem cell factor (SCF) receptor c-Kit regulates vascular smooth muscle cell (SMC) phenotype and is potently anti-atherogenic. Methods and Results: Atherosclerotic plaque was quantified in transgenic mice deficient for c-Kit (c-KitW/Wv ApoE-/-) or SCF (c-Kitlsl/+ ApoE-/-) after 16 weeks of high fat diet (HFD). Both mutant strains displayed substantially greater atherosclerosis compared with control (ApoE-/-) littermates (pu003c0.01 and u003c0.05 respectively). Transplantation of c-Kit positive bone marrow into c-KitW/Wv ApoE-/- mice failed to rescue the atherogenic phenotype indicating that increased atherosclerosis was associated with reduced arterial c-Kit. To investigate the mechanism, SMC organization and morphology were analyzed in aorta by histopathology and electron microscopy. Remarkably, SMCs were more abundant, disorganized and vacuolated in aortas of c-Kit mutant mice compared with controls (pu003c0.05). Markers of the “contractile” SMC phenotype (Ca...