Abstract 14889: Ckit Expression in Vascular Smooth Muscle Cells Protects Mice Against Excessive Atherosclerosis
Introduction: We have previously demonstrated that global deficiency of cKit, an important receptor tyrosine kinase, exacerbates atherosclerosis in hyperlipidemic mice. This study aims at demonstrating the protective role of c-Kit in smooth muscle cells (SMCs) against atherogenesis, and the mechanism underlying.
Methods and Results: Atherosclerosis was assessed in triple transgenic mice with cKit targeted deletion in SMCs. In this model, atherosclerotic burden was significantly increased in c-Kit deficient mice versus control littermates. The loss of cKit was associated with medial SMCs hypertrophy, hypercellularity, and reduced expression of “contractile” proteins in aortas. In vitro, cKit-deficient aortic SMCs proliferated faster and migrated more than those from wild type controls. The absence of cKit made SMCs prone to acquire a foam-like phenotype secondary to increased activity of the Kruppel like factor 4 (KLF4), a transcriptional factor that favors SMC pathological synthetic phenotype. Rescue of cKit in deficient SMCs led to decreased level of KLF4, restored contractile markers, and prevented foam cell formation.
Conclusion: This study provides mechanistic evidence that vascular cKit is involved in controlling SMCs phenotype and is atheroprotective in hyperlipidemic mice.
Author Disclosures: L. Song: None. G. Selman: None. N. Santos: None. L. Martinez: None. R.M. Lassance-Soares: None. K. Webster: None. R. Vazquez Padron: None.
- © 2016 by American Heart Association, Inc.