Interactions between β3‐adrenergic receptors and bFGF‐induced effects in rat aortic smooth muscle cells

Abstract

BackgroundBasic 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 β3‐adrenergic receptors (β3‐ARs) in vascular injury‐induced neointima formation has not yet been defined.ObjectivesOur current study explored the possible role of β3‐ARs in vascular injury‐induced neointima formation by testing its effects on bFGF‐induced VSMC migration and proliferation.Methodsβ3‐AR expression in rat carotid arteries was examined at 14 days following a balloon catheter‐induced injury. The effects of β3‐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.ResultsWe found that vascular injury induced upregulation of β3‐ARs in neointima. Pretreatment of VSMCs with a selective β3‐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.ConclusionOur results suggest that activation of β3‐ARs enhances bFGF‐mediated effects on VSMCs by interacting with bFGF‐mediated ERK and AKT phosphorylation and β3‐ARs may play a role in vascular injury‐induced neointima formation.