Increased synthetic phenotype behavior of smooth muscle cells in response to in vitro balloon angioplasty injury model

Abstract

Restenosis remains a common problem following balloon angioplasty, and it has been speculated that changes in the mechanical environment due to endovascular interventions are correlated with shifts in smooth muscle cell (SMC) phenotype. In order to study SMC response to forces similar to those exerted during balloon angioplasty, an in vitro concurrent shear and tensile forces simulator has been developed. After 24 hr of exposure to cyclic tension (5%) and shear (0.1-0.5 dynes/cm(2)) following simulated angioplasty injury (12% stretch), rat aortic SMCs exhibited significant synthetic behavior. These responses included increased cell proliferation, apoptosis, and cell hypertrophy compared to cells exposed to strain alone. While all SMCs exposed to dynamic stimuli (strain, strain+balloon injury, strain+balloon injury+shear) demonstrated a decrease in contractile protein expression, the injury group also exhibited significantly greater expression of the synthetic marker vimentin. These in vitro findings agree with in vivo events following balloon angioplasty and present a refined dynamic model to be implemented for better understanding of SMC activation and prevention of responses through pharmacological treatment.