Circulating and Tissue Endothelin Immunoreactivity in Advanced Atherosclerosis

Background. Atherosclerosis is characterized by endothelial injury and the proliferation of arterial smooth-muscle cells. The latter may be a result of the release of growth factors from the vessel wall; such growth factors may include an endothelium-derived vasoconstrictor peptide with mitogenic properties. We tested the hypothesis that plasma endothelin concentrations are elevated in persons with symptomatic atherosclerosis, independently of age. Methods. We measured plasma endothelin levels in 100 normal subjects and in 40 patients with atherosclerosis predominantly of the following types: aortic and peripheral vascular disease (14 patients), renovascular disease (9 patients), coronary artery disease (9 patients), and carotid disease (8 patients). We also performed immunohistochemical staining for endothelin in the walls of atherosclerotic vessels. Results. In the normal subjects, the mean (±SD) plasma endothelin concentration was 1.4±0.2 pmol per liter, with no correlation between age and plasma endothelin concentration (r = 0.13, P = 0.2). In the patients with symptomatic atherosclerosis, the mean plasma endothelin concentration was 3.2±1.2 pmol per liter (P<0.001), and there was a significant correlation between plasma endothelin and the number of sites of disease involvement (r = 0.89, P<0.001). In the immunohistochemical studies, endothelin-1-like immunoreactivity was observed in vascular smooth muscle as well as in endothelial cells. Conclusions. Endothelin may be a marker for arterial vascular disease. Whether it participates in the atherogenic process or is merely released from damaged endothelial cells is unclear. (N Engl J Med 1991;325:997–1001.)