Regulation of bFGF-induced effects on rat aortic smooth muscle cells by β(3)-adrenergic receptors

BACKGROUND: Basic fibroblast growth factor (bFGF)-mediated vascular smooth muscle cell (VSMC) proliferation and migration play an important role in vascular injury-induced neointima formation and subsequent vascular restenosis, a major event that hinders the long-term success of angioplasty. The function of β(3)-adrenergic receptors (β(3)-ARs) in vascular injury-induced neointima formation has not yet been defined. OBJECTIVES: Our current study explored the possible role of β(3)-ARs in vascular injury-induced neointima formation by testing its effects on bFGF-induced VSMC migration and proliferation. METHODS: β(3)-AR expression in rat carotid arteries was examined at 14 days following a balloon catheter-induced injury. The effects of β(3)-AR activation on bFGF-induced rat aortic smooth muscle cell proliferation, migration, and signaling transduction (including extracellular-signal-regulated kinase/mitogen activated protein kinase, ERK/MAPK and Protein kinase B, AKT) were tested. RESULTS: We found that vascular injury induced upregulation of β(3)-ARs in neointima. Pretreatment of VSMCs with a selective β(3)-AR agonist, CL316,243 significantly potentiated bFGF-induced cell migration and proliferation, and ERK and AKT phosphorylation. Our results also revealed that suppressing phosphorylation of ERK and AKT blocked bFGF-induced cell migration and that inhibiting AKT phosphorylation reduced bFGF-mediated cell proliferation. CONCLUSION: Our results suggest that activation of β(3)-ARs potentiates bFGF-mediated effects on VSMCs by enhancing bFGF-mediated ERK and AKT phosphorylation and that β(3)-ARs may play a role in vascular injury-induced neointima formation.