Development of a novel vascular simulator and injury model to evaluate smooth muscle cell response following balloon angioplasty

Following balloon angioplasty, denudation of endothelial cells exposes vascular smooth muscle cells (SMCs) to normally unseen shear forces from blood flow. In vivo studies investigate the response to angioplasty injury, but limited studies have been performed using in vitro systems. In order to study SMC response in vitro, a concurrent shear and tensile forces simulator has been developed to provide clinically significant levels of strain and shear stresses in addition to simulating forces similar to those during balloon angioplasty. In this acute study (8 hr), rat aortic SMCs demonstrated significant cell proliferation following applied increased tensile forces of angioplasty injury and shear exposure when compared to lower levels of tensile exposure similar to a normal physiological level, with an average 75% increase in the number of cells of the injury group compared to the normal dynamic group. SMCs exposed to balloon angioplasty injury and concurrent shear and tensile mechanical forces demonstrated decreased expression of the contractile phenotypic marker smooth muscle alpha-actin. These findings demonstrate the efficacy of the developed model for in vitro angioplasty and the simulated mechanical environment to the cells. This provides an in vitro model to isolate the effects of concurrent mechanical forces and could also potentially act as a preliminary step toward use in pharmaceutical research for reduction or prevention of SMC proliferation due to altered mechanical forces during endovascular procedures.