Endothelin-1 and its receptor in hypertrophic cardiomyopathy.
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.
Hasegawa
K
K
Department of Medicine, University School of Medicine, Kyoto, Japan.
Fujiwara
H
H
Koshiji
M
M
Inada
T
T
Ohtani
S
S
Doyama
K
K
Tanaka
M
M
Matsumori
A
A
Fujiwara
T
T
Shirakami
G
G
Hosoda
K
K
Nakao
K
K
Sasayama
S
S
D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D006328:Cardiac Catheterization; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016232:Endothelins / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006352:Heart Ventricles; D006439:Hemodynamics; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017466:Receptors, Endothelin / Q000032:analysis / Q000096:biosynthesis*; D012016:Reference Values; D012044:Regression Analysis
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016232:Endothelins; D012333:RNA, Messenger; D017466:Receptors, Endothelin