RAISED PLASMA ENDOTHELIN-1 CONCENTRATIONS IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA WITHOUT EVIDENCE OF ATHEROSCLEROSIS

The present study was designed to investigate the pattern of circulati ng endothelin-1 (ET-1), a potent vasoconstricting mitogenic endotheliu m-derived peptide, in relation to primary increase in serum cholestero l in humans. We measured plasma ET-1 concentrations by radioimmunoassa y (Amersham, UK) in 8 patients (6 females and 2 males, aged 42-62 year s) with primary hypercholesterolemia, non-smokers, without evidence of cardiovascular disease, and in 8 healthy sex-and age-matched control subjects. The mean (+/- SD) values of serum total cholesterol, low-den sity-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cho lesterol and triglycerides in the hypercholesterolemic subjects were 7 .2 +/- 1.1 mmol/L, 5.1 +/- 1.1 mmol/L, 1.0 +/- 0.1 mmol/L and 2.4 +/- 0.9 mmol/L, respectively. The lipid profile of the controls showed a t otal cholesterol of 4.6 +/- 0.3 mmol/L, LDL cholesterol of 3.0 +/- 0.2 mmol/L, HDL cholesterol of 1.0 +/- 0.1 mmol/L and triglycerides of 1. 2 +/- 0.2 mmol/L. The mean ET-1 plasma levels in the hypercholesterole mic patients were significantly higher than in the controls (4.2 +/- 0 .1 pmol/L, and 2.2 +/- 0.7 pmol/L, respectively, p < 0.001). Our data of raised circulating ET-1 in hypercholesterolemic patients without ev idence of atherosclerosis suggest that an exaggerated release of ET-1 could contribute: 1) to impair endothelium-dependent vasodilation; 2) to promote the atherogenic process in hypercholesterolemia. Finally, i t could represent a marker for hypercholesterolemic endothelial damage .