Strain and Strain Rate Dependence of Vascular Smooth Muscle Injury

Over 350,000 percutaneous translumenal coronary angioplasty (balloon angioplasty) procedures are performed each year. This procedure offers a less invasive alternative to coronary by-pass surgery for patients whose coronary vessels have become occluded due to the process of atherosclerosis. Its potential has not been fully realized due to the high rate of restenosis — the rapid reocclusion of the vessel due to the pathological growth of the vascular smooth muscle (VSM) in response to the trauma of the balloon inflation. Despite the recognition of smooth muscle injury as an initiating event in the process of restenosis, there has been no systematic study to determine the mechanical loading conditions required to produce VSM injury and elicit the restenosis response. In this study, a cell culture model was developed to define the loading conditions required to produce VSM injury. The model system allows precise control of the applied strain and strain rate and quantification of the injury severity in terms of membrane damage. The determination of the threshold criteria for cell injury will allow the angioplasty procedure to be modified, and possibly automated, to minimize VSM injury and avoid the restenosis response.