The endothelium as a regulator of vascular smooth muscle proliferation

Abstract

In the mature blood vessel wall, smooth muscle cells are responsible for the maintenance of vascular tone and exhibit very little proliferative activity. Damage to the endothelium results in activation of smooth muscle cell proliferative behavior. Repair of the endothelium leads to the reversal of this process and restoration of smooth muscle cell quiescence. This sequence of events is indicative of a major role of the endothelium in the regulation of vascular smooth muscle cell growth. Most studies of the mechanisms of endothelium-dependent growth regulation have focused on growth stimulation rather than on the consequences of impaired growth inhibition. Thus, the identification of endothelium-derived growth inhibitory compounds has lagged behind the characterization of growth stimulators that impinge on smooth muscle proliferative metabolism. Endothelium-derived heparinoids are inhibitory to smooth muscle cell growth and currently remain the only clearly identified growth regulators of endothelial cell origin. Elevation of intracellular cGMP in smooth muscle cells mediates both their relaxation and inhibition of proliferation. Endothelium-derived relaxing factor, which has been identified as nitric oxide or a labile donor of the same, mediates its physiological effect on smooth muscle cells by the elevation of intracellular cGMP. It remains to be demonstrated that this same action of nitric oxide also results in the depression of smooth muscle cell growth.