Abstract 542: Dedicator of Cytokinesis 2 (DOCK2) Promotes Vascular Lesion Formation through Stimulation of Smooth Muscle Cell Proliferation and Migration
The objective of this study is to determine the role of dedicator of cytokinesis 2 (DOCK2) in vascular lesion formation after experimental angioplasty. By using a rat carotid artery balloon-injury model, we demonstrate that neointima formation is closely associated with DOCK2 expression. DOCK2 is not expressed in normal arteries. However, its expression was observed in the developing neointima and media after injury as shown by immunohistochemistry staining, qPCR and Western blot analyses. shRNA knockdown of DOCK2 via adenovirus (Ad)-mediated gene delivery dramatically inhibited the neointimal formation by 65% as compared to those treated with control shRNA or saline. Similar results were obtained when intima/media area ratios were compared between DOCK2 knockdown and control groups. Loss of function studies in primary culture of rat aortic smooth muscle cells (RASMCs) indicated that DOCK2 is essential for both the proliferation and migration of RASMCs. PDGF-BB induced DOCK2 expression in RASMCs. shRNA knockdown of DOCK2 significantly inhibited PDGF-BB-induced proliferation and migration of RASMCs. DOCK2 appeared to stimulate RASMC migration via inducing focal adhesion contact and stress fiber formation as shown by the altered expression of vinculin and F-actin, respectively. Taken together, our studies demonstrate that DOCK2 plays an important role in vascular lesion formation following vascular injury. Therefore, targeting DOCK2 is a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases.
- © 2013 by American Heart Association, Inc.