Abstract 442: YY1 (Yin Yang Factor 1) Is Induced in Injured Vessel Wall Including Aortic Aneurysms and Suppresses Vascular Smooth Muscle Cell Differentiation Through Disrupting Myocardin-mediated Transcriptional Regulation

Abstract

Vascular smooth muscle cell (VSMC) differentiation is essential for normal vascular function. Its phenotypic plasticity plays a major role in the pathogenesis of vascular diseases. SMC differentiation is marked by the expression of a variety of SMC marker genes controlled by corporative interactions between SMC key transcription factor Myocardin and Serum Response Factor (SRF). Previous studies showed that YY1 (Yin Yang- factor 1, a multifunctional versatile transcription factor) inhibits SMC growth and intimal thickening. However, the role of YY1 in SMC differentiation has been controversial and not characterized. We observed increased YY1 expression in injured vessel wall including aortic aneurysms, suggesting its roles in SMC phenotypic modulation. To determine the roles of YY1 in SMC differentiation, we found that YY1 negatively regulates the expression of SMC marker genes in cultured VSMCs: YY1 overexpression suppresses the transcription of SMC-specific marker genes including Sm22(Tagln) and Acta2 whereas its knockdown increased their transcription. YY1 also suppressed Myocardin transcription and its promoter activation. Mechanistically, we found that YY1 interacts with Myocardin and disrupts its interaction with SRF in the CArG box of SMC gene promoters. This work provides new mechanistic insights of YY1 in SMC phenotypic modulation that leads to pathogenesis of vascular diseases.