ABSTRACT
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 ß3-adrenergic receptors (ß3-ARs) in vascular injury-induced neointima formation has not yet been defined. Objectives: Our current study explored the possible role of ß3-ARs in vascular injury-induced neointima formation by testing its effects on bFGF-induced VSMC migration and proliferation. Methods: ß3-AR expression in rat carotid arteries was examined at 14 days following a balloon catheter-induced injury. The effects of ß3-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 ß3-ARs in neointima. Pretreatment of VSMCs with a selective ß3-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 ß3-ARs potentiates bFGF-mediated effects on VSMCs by enhancing bFGF-mediated ERK and AKT phosphorylation and that ß3-ARs may play a role in vascular injury-induced neointima formation.
