Endothelin-1 and Its Receptor in Hypertrophic Cardiomyopathy

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 cardio...