Elevated endothelin levels in patients with hyperlipoproteinemia

Abstract

We determined lipoproteins, apolipoproteins, and endothelin in 98 patients (58 female and 40 male, age 18-72 years) with hyperlipidemia (plasma cholesterol > 2.5 g/l and/or triglycerides > 2.0 g/l) and in 50 healthy subjects (20 female, 30 male, age 19-68 years). In patients with hyperlipidemia endothelin levels were elevated compared to healthy controls. Patients with plasma cholesterol above 2.5 g/l had higher endothelin and lipoprotein(a) concentrations than patients with plasma cholesterol levels less than 2.5 g/l. A positive correlation was found between the concentrations of endothelin and apolipoprotein B (r = 0.2137; P < 0.013). Smoking patients with lipoprotein (a) above 300 mg/l had higher endothelin levels than both nonsmoking patients with lipoprotein (a) above 300 mg/l and smokers with normal lipoprotein(a). In smokers endothelin correlated positively with Lp(a) (r = 0.709; P < 0.01). No correlation was found between endothelin and triglycerides nor between endothelin and age or sex. The results suggest that the vasoconstrictor endothelin contributes to the increased vasal tone in hyperlipidemia. Because endothelin also has mitogenic properties, it may play a relevant role in the development of premature atherosclerosis in patients with hyperlipidemia.

Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome

“…On the other hand, data exist that elevated circulating ET levels exert pathophysiological effects contributing to development of hypertension, atherosclerosis and coronary artery vasoconstriction. Moreover, the vasoconstrictor effect of ET increases vascular tone in hyperlipidemic patients (15). The significant correlation observed between elevated ET and serum cholesterol in Cushing's syndrome points to a hypothetical role of ET as a humoral atherogenic factor enhancing atherosclerotic processes and endothelial dysfunction in hypercorticism.…”

“…The rather high ET levels in patients dying subsequently, support the idea of ET as a risk factor and predictor of severe, even lethal cardiovascular complications. It has been proved that in patients with high cholesterol levels ET and lipoprotein (a) are likewise elevated (15). Glucocorticosteroids stimulate the release of ET by vascular smooth muscle cells, and thus exert a permissive effect on the local atherogenic and hypertensive ET action.…”

Role of phosphoinositide 3-kinase in the nonselective cation channel activation by endothelin-1/endothelinBreceptor

“…It is generally accepted that ET-1 may play a role in the pathogenesis of certain clinical conditions such as hyperlipoproteinemia, atherosclerosis, stroke, cerebral vasospasm, and tumor growth (2,9). We demonstrated recently that the extracellular Ca 2ϩ influx is required to ET-1-induced vascular contraction and mitogenesis (4,6).…”

Chronic Endothelin Receptor Antagonism Preserves Coronary Endothelial Function in Experimental Hypercholesterolemia

“…30,31 It is increased in patients with atherosclerotic risk factors including hypercholesterolemia and is increased locally within atherosclerotic plaques. 10,32,33 This peptide also mediates the response to vascular injury and promotes restenosis after balloon catheter injury. 13,34 Moreover, selective ET-A receptor antagonism decreases the development of atherosclerosis caused by cholesterol feeding, and chronic ET-A receptor antagonism inhibits neointimal hyperplasia after both balloon and stent injury.…”