Raised plasma endothelin-1 concentrations in patients with primary hypercholesterolemia without evidence of atherosclerosis

The present study was designed to investigate the pattern of circulating endothelin-1 (ET-1), a potent vasoconstricting mitogenic endothelium-derived peptide, in relation to primary increase in serum cholesterol in humans. We measured plasma ET-1 concentrations by radioimmunoassay in 8 patients (6 females and 2 males, aged 42-62 years) 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-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol 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 total 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 hypercholesterolemic 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 evidence 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, it could represent a marker for hypercholesterolemic endothelial damage.