Response gene to complement 32 promotes vascular lesion formation through stimulation of smooth muscle cell proliferation and migration.

OBJECTIVE: The objectives of this study were to determine the role of response gene to complement 32 (RGC-32) in vascular lesion formation after experimental angioplasty and to explore the underlying mechanisms. METHODS AND
RESULTS: Using a rat carotid artery balloon-injury model, we documented for the first time that neointima formation was closely associated with a significantly increased expression of RGC-32 protein. Short hairpin RNA knockdown of RGC-32 via adenovirus-mediated gene delivery dramatically inhibited the lesion formation by 62% as compared with control groups 14 days after injury. Conversely, RGC-32 overexpression significantly promoted the neointima formation by 33%. Gain- and loss-of-function studies in primary culture of rat aortic smooth muscle cells (RASMCs) indicated that RGC-32 is essential for both the proliferation and migration of RASMCs. RGC-32 induced RASMC proliferation by enhancing p34(CDC2) activity. RGC-32 stimulated the migration of RASMC by inducing focal adhesion contact and stress fiber formation. These effects were caused by the enhanced rho kinase II-α activity due to RGC-32-induced downregulation of Rad GTPase.
CONCLUSIONS: RGC-32 plays an important role in vascular lesion formation following vascular injury. Increased RGC-32 expression in vascular injury appears to be a novel mechanism underlying the migration and proliferation of vascular smooth muscle cells. Therefore, targeting RGC-32 is a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases.