INCREASED ENDOTHELIN PLASMA-CONCENTRATIONS IN PATIENTS WITH CORONARY-ARTERY DISEASE OR HYPERLIPOPROTEINEMIA WITHOUT CORONARY EVENTS

Endothelins are made by endothelial cells, macrophages, and vascular s mooth muscle cells, among others, and are the most potent endogenous v asoconstrictors yet discovered, with additional growth-promoting prope rties. A locally increased endothelin production in coronary artery di sease or other atherosclerotic diseases may increase circulating endot helin plasma concentrations before symptoms of disease are manifest. W e determined endothelin plasma concentrations (1) in 43 patients suffe ring from coronary artery disease (CAD); (2) in 43 patients with hyper lipoproteinemia without coronary artery disease (HLP); (3) in 29 healt hy control subjects (C), by means of a novel extraction procedure and radioimmunoassay followed by chromatographic separation. Plasma concen trations in HLP and C overlapped, but were still significantly differe nt (29 +/- 10 vs 21 +/- 8 fmol/ml, ANOVA and Duncan's test). Significa ntly increased plasma concentrations were also found in patients with CAD, with the highest levels in a subgroup of 8 patients presenting wi th unstable angina (43 +/- 12 vs 53 +/- 15 fmol/ml). There were no sta tistically significant differences between CAD groups with (n = 28) or without hyperlipoproteinemia (n = 15) (42 +/- 14 vs 41 +/- 16 fmol/ml ; n.s.). Likewise there was no relationship between endothelin plasma concentration in any of the patients studied and lipid fractions in se rum. Increased endothelin plasma concentrations in HLP patients withou t evidence of coronary artery disease are thus not related to the hype rlipidemic state per se, but may rather indicate presence of an increa sed vasoconstrictor tonus, pre-clinical or silent atherosclerotic dise ase.