Cell biology of human vascular smooth muscle

Vascular smooth muscle is the cellular substrate of most significant arterial diseases. Restenosis after angioplasty and surgery mainly represents vascular smooth muscle reaction to trauma, a process which is also significant in the early stages of atherogenesis. Empirical approaches, based on findings in animal models of vascular injury, have notably failed to make any impact on human restenosis. We have developed and validated growth of the human VSMC in culture as a model of restenosis. Intimal hyperplastic lesions producing vascular restenosis contain cells that have reduced sensitivity to physiological growth inhibition by heparin in cell culture conditions, compared with cells from normal vascular tissue. Undiseased saphenous vein obtained from patients with intimal hyperplastic restenoses also contain cells that are relatively resistant to heparin inhibition. Arterial healing that progresses to restenosis may have distinct and fundamental differences at the cellular level from the normal process of arterial healing after injury.