Abstract 189: The Zinc-finger Protein 148(zfp148) Modulates Smooth Muscle Marker Genes via Interaction With Nf-1 in Vascular Disease

Objective: We and others have shown that smooth muscle (SMC) marker gene down-regulation is an early event in vascular disease and involves the transcription factor KLF4. However, the molecular mechanisms mediating continued repression following KLF4 release remain unknown. Recently, we have shown that ZFP148 is critical in SMCs during aortic aneurysm formation; however, no studies have investigated the molecular mechanisms of this process. The study objective was to determine what factors mediate SMC down-regulation after KLF4 binding is diminished. Methods and Results: 8-12 week male mice (n=8 per group) underwent carotid ligation and were harvested at day 7 for chromatin immunoprecipitation analysis (ChIP) for KLF4, KLF2, ZFP148, NF-1, Sp1, Sp3 and YY1. ZFP148, NF-1 and KLF2 were significantly elevated following ligation injury. In separate experiments, 8-12 week male (n=10/group) C57/B6 mice underwent carotid ligation and were harvested at 1, 3, 7, and 14, days for ChIP analysis for ZFP148 and NF-1. Z...