Regulation of bFGF-induced effects on rat aortic smooth muscle cells by β-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-adrenergic receptors (β-ARs) in vascular injury-induced neointima formation has not yet been defined.

OBJECTIVES

Our current study explored the possible role of β-ARs in vascular injury-induced neointima formation by testing its effects on bFGF-induced VSMC migration and proliferation.

METHODS

β-AR expression in rat carotid arteries was examined at 14 days following a balloon catheter-induced injury. The effects of β-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-ARs in neointima. Pretreatment of VSMCs with a selective β-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-ARs potentiates bFGF-mediated effects on VSMCs by enhancing bFGF-mediated ERK and AKT phosphorylation and that β-ARs may play a role in vascular injury-induced neointima formation.