Abstract 9922: The Induction of YAP Expression Following Arterial Injury is Crucial for Smooth Muscle Phenotypic Modulation and Neointima Formation
Rationale: Abnormal proliferation and migration of vascular smooth muscle cells (SMCs) are the key events in the progression of neointimal formation in response to vascular injury. Previous studies have shown that YAP is a potent oncogene promoting cell migration and proliferation, while the role of YAP in vascular diseases remain unknown.
Objective: The goal of this study is to investigate the functional role of YAP in smooth muscle phenotypic modulation in vitro and in vivo.
Methods and Results: In vitro in cell culture and in vivo in both mouse and rat arterial injury models YAP expression is significantly induced and correlated with the vascular SMC synthetic phenotype. YAP is also highly expressed in human carotid atherosclerotic plaque and localized in the majority of SMCs. Over-expression of YAP promotes SMC migration and proliferation while attenuating smooth muscle contractile gene expression. Conversely, knocking-down endogenous YAP in SMCs up-regulates smooth muscle gene expression but attenuates SMC proliferation and migration. Consistent with this, knocking-down YAP expression in a rat carotid balloon injury model attenuates injury-induced smooth muscle dedifferentiation and neointima formation. Furthermore, carotid artery ligation in mice with genetic deletion of YAP specifically in SMCs leads to increase smooth muscle-specific gene expression and reduction of neointima formation.
Conclusion: YAP plays a novel integrative role in smooth muscle phenotypic modulation by inhibiting smooth muscle-specific gene expression while promoting smooth muscle proliferation and migration in vitro and in vivo. Blocking the induction of YAP would be a potential therapeutic approach for ameliorating vascular occlusive diseases.
- © 2012 by American Heart Association, Inc.