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Endothelin-1 and its receptor in hypertrophic cardiomyopathy
K Hasegawa1, H Fujiwara, M Koshiji
1Department of Medicine, University School of Medicine, Kyoto, Japan.
Insights
Plasma levels of endothelin-1 were significantly elevated in patients with hypertrophic cardiomyopathy, suggesting its potential role in this heart condition. Further research is needed to determine if endothelin-1 causes or merely marks cardiac hypertrophy.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
Background:
- Endothelin-1, a vasoconstrictor, is known to activate cardiac hypertrophy in cell cultures.
- The specific role of endothelin-1 in human cardiac hypertrophy remains unclear.
Purpose of the Study:
- To investigate the involvement of endothelin-1 in human hypertrophic cardiomyopathy.
- To compare endothelin-1 levels and receptor expression in patients versus controls.
Main Methods:
- Radioimmunoassay was used to measure plasma endothelin-1 levels.
- In situ hybridization analyzed endothelin-1 type A receptor mRNA in endomyocardial biopsies.
Main Results:
- Hypertrophic cardiomyopathy patients exhibited more than double the plasma endothelin-1 levels compared to controls.
- Endothelin-1 type A receptor mRNA expression in ventricular myocytes was similar between groups.
Conclusions:
- Elevated endothelin-1 may be an important factor in hypertrophic cardiomyopathy.
- Further studies are required to establish a causal link or confirm endothelin-1 as a marker for cardiac hypertrophy.
Abstract:
Endothelin-1, a potent vasoconstrictor produced by vascular endothelial cells, activates the hypertrophic program in cultured heart muscle cells. However, the role of endothelin-1 in cardiac hypertrophy in humans is unknown. Therefore, we studied hypertrophic cardiomyopathy patients with normal pulmonary arterial pressure, in whom cardiac hypertrophy is a specific feature of the disease. Radioimmunoassay with a monoclonal antibody to human endothelin-1 showed that the plasma level of immunoreactive endothelin was more than twofold higher in hypertrophic cardiomyopathy patients than in control subjects (P < .005). In situ hybridization analysis of endomyocardial biopsy specimens showed positive signals of endothelin-1 type A receptor mRNA in ventricular myocytes of all specimens. The receptor expression in ventricular myocytes was similar between hypertrophic cardiomyopathy patients and control subjects. We propose that endothelin-1 might represent an important factor involved in hypertrophic cardiomyopathy. Whether endothelin-1 plays a causal role in cardiac hypertrophy or is a marker of its occurrence needs to be clarified.