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Increased endothelin plasma concentrations in patients with coronary artery disease or hyperlipoproteinemia without
R M Arendt1, U Wilbert-Lampen, L Heucke
1Medizinische Klinik I, Ludwig-Maximilians-Universität, Klinikum Grosshadern, München, Germany.
Insights
Elevated endothelin plasma concentrations were observed in patients with coronary artery disease (CAD) and hyperlipoproteinemia (HLP). These findings suggest increased vasoconstrictor tone and potential pre-clinical atherosclerotic disease in HLP patients.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Biochemistry
Background:
- Endothelins are potent vasoconstrictors produced by various cells, including endothelial cells and macrophages.
- Increased local endothelin production in atherosclerotic diseases may precede clinical symptoms.
- Endothelins possess growth-promoting properties relevant to vascular health.
Purpose of the Study:
- To measure plasma endothelin concentrations in patients with coronary artery disease (CAD) and hyperlipoproteinemia (HLP) without CAD.
- To compare endothelin levels between patient groups and healthy controls.
- To investigate the relationship between endothelin levels, hyperlipidemia, and atherosclerotic disease.
Main Methods:
- Novel extraction procedure and radioimmunoassay followed by chromatographic separation were employed.
- Plasma endothelin concentrations were determined in 43 CAD patients, 43 HLP patients, and 29 healthy controls.
- Statistical analysis included ANOVA and Duncan's test for group comparisons.
Main Results:
- Significantly elevated endothelin plasma concentrations were found in CAD patients compared to controls (53 +/- 15 fmol/ml vs 21 +/- 8 fmol/ml).
- HLP patients also showed higher endothelin levels than controls (29 +/- 10 fmol/ml vs 21 +/- 8 fmol/ml).
- No correlation was found between endothelin levels and serum lipid fractions in any patient group.
Conclusions:
- Increased endothelin plasma concentrations are associated with coronary artery disease.
- Elevated endothelin in HLP patients without CAD may indicate increased vasoconstrictor tone or subclinical atherosclerotic disease.
- Endothelin levels in HLP are not directly related to the hyperlipidemic state itself.
Abstract:
Endothelins are made by endothelial cells, macrophages, and vascular smooth muscle cells, among others, and are the most potent endogenous vasoconstrictors yet discovered, with additional growth-promoting properties. A locally increased endothelin production in coronary artery disease or other atherosclerotic diseases may increase circulating endothelin plasma concentrations before symptoms of disease are manifest. We determined endothelin plasma concentrations (1) in 43 patients suffering from coronary artery disease (CAD); (2) in 43 patients with hyperlipoproteinemia without coronary artery disease (HLP); (3) in 29 healthy control subjects (C), by means of a novel extraction procedure and radioimmunoassay followed by chromatographic separation. Plasma concentrations in HLP and C overlapped, but were still significantly different (29 +/- 10 vs 21 +/- 8 fmol/ml, ANOVA and Duncan's test). Significantly increased plasma concentrations were also found in patients with CAD, with the highest levels in a subgroup of 8 patients presenting with unstable angina (43 +/- 12 vs 53 +/- 15 fmol/ml). There were no statistically 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 serum. Increased endothelin plasma concentrations in HLP patients without evidence of coronary artery disease are thus not related to the hyperlipidemic state per se, but may rather indicate presence of an increased vasoconstrictor tonus, pre-clinical or silent atherosclerotic disease.