Abstract 227: TGF-β/Smad3 Promotes Smooth Muscle Cell De-differentiation and Proliferation Through Crosstalk with the Wnt/β-Catenin Pathway

Introduction: Endovascular interventions are the first line treatment for patients with atherosclerotic disease. However, a significant number of these fail due to neointimal hyperplasia. The Wnt4/β-catenin pathway has been reported to play an important role in this process, but the mechanism underlying the up-regulation of this pathway after injury remains unclear. Our lab has previously demonstrated that following vascular injury, elevated TGF-β and its signaling protein, Smad3, exacerbate intimal hyperplasia in Smooth Muscle Cells (SMCs). Moreover, our Affymetrix array data revealed an upregulation (>3 fold) of several members of the Wnt family in response to TGF-β/Smad3 treatment of SMCs. Therefore, we hypothesize that the TGF-β/Smad3 axis is responsible for the activation of the Wnt/β-catenin signaling pathway that promotes neointimal hyperplasia. Methods and Results: To mimic the injury induced up-regulation of TGF-β/Smad3 in vitro, SMCs were infected with an adenovirus to increase Smad3 and then tr...