Mechanisms of vascular atrophy and fibrous cap disruption

The process of plaque destabilization and rupture remains an area of intense investigation. While reductions in lumen cross-sectional area induced by early, non-occlusive lesions are compensated by remodeling and expansion of the artery, further plaque enlargement leads to an uncompensated reduction in lumen area and an increase in surface shearing forces. We hypothesize that these local increases in wall shear stress lead to a reduction in smooth muscle cell proliferation and increase in cell death. Using a primate prosthetic graft model, we have observed that alterations in nitric oxide and platelet-derived growth factor metabolism are important regulators of intimal growth and regression. We suggest that these factors may also be influential in the process of fibrous cap atrophy and plaque rupture.