Direct comparison of endothelial cell and smooth muscle cell response to supercooling and rewarming

Restenosis is a major limitation of percutaneous transluminal angioplasty for peripheral vascular disease. Although the underlying mechanisms are not well understood, it is generally believed that arterial recoil and neointimal hyperplasia in the setting of thrombus formation, matrix overproduction, and smooth muscle cell (SMC) migration and proliferation play significant roles. Cryoplasty, which combines mechanical dilatation of the vessel wall with the delivery of cold thermal energy, has been recently developed. We hypothesize that cryoplasty, apart from the mechanical force, exerts a thermal effect on the vessel wall that may influence cellular proliferation and survival. In this study, we directly compared the effects of supercooling and rewarming on bovine aortic SMC and endothelial cell (EC) apoptosis and proliferation in a model simulating the temperature changes induced by cryoplasty. We definitively demonstrated that the apoptotic rate of ECs is significantly less than that of SMCs under the same conditions, although the apoptotic rate of both increased with increasing supercooling and rewarming. These results provide several potential mechanisms for the lower restenosis rates reported with cryoplasty.