Related Experiment Video
Updated: Oct 25, 2026
A Neonatal Heterotopic Rat Heart Transplantation Model for the Study of Endothelial-to-Mesenchymal Transition
Published on: July 21, 2023
Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian
T Inada1, H Fujiwara, K Hasegawa
1Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Japan.
Insights
Endogenous endothelin-1 (ET-1) significantly increases in the hearts of cardiomyopathic hamsters, contributing to pathological myocyte growth. Blocking the ET-1 pathway with T0201 reduced this growth but did not impact fibrosis.
Area of Science:
- Cardiovascular Research
- Molecular Cardiology
- Animal Models of Disease
Background:
- Endothelin-1 (ET-1) is a peptide implicated in cardiac hypertrophy.
- The role of endogenous ET-1 in primary myocardial disease remains unclear.
Purpose of the Study:
- To investigate the role of endogenous endothelin-1 (ET-1) in myocardial growth.
- To assess the impact of ET-1 on cardiac pathology in Syrian cardiomyopathic hamsters.
Main Methods:
- Measured left ventricular ET-1 levels using ELISA.
- Administered T0201, an ET type A receptor antagonist, to assess its chronic effects.
- Utilized immunohistochemistry to localize ET-1 in cardiac myocytes.
Main Results:
- ET-1 levels were significantly elevated in the hearts of cardiomyopathic hamsters compared to controls.
- T0201 treatment reduced heart weight/body weight ratio and myocyte diameter in cardiomyopathic hamsters.
- T0201 did not affect fibrosis in either group.
Conclusions:
- Cardiac ET-1 levels increase in a stage-dependent and organ-specific manner in this model.
- Accelerated ET-1 synthesis contributes to pathological myocyte growth, not degeneration or fibrosis.
- The ET-1 pathway is a potential therapeutic target for managing cardiac growth in specific cardiomyopathies.
Objectives:
The purpose of this study is to investigate the role of endogenous endothelin-1 (ET-1) in myocardial growth in Bio 14.6 Syrian cardiomyopathic hamsters (Bio).
Background:
While ET-1, as a growth-promoting peptide, has been implicated in the development of secondary cardiac hypertrophy, the role of endogenous ET-1 in cardiac growth in primary myocardial disease is unknown.
Methods:
We measured left ventricular ET-1 levels by a specific sandwich enzyme-linked immunosorbent assay. Furthermore, we examined the chronic effect of T0201, an ET type A receptor-specific antagonist.
Results:
The ET-1 levels in the left ventricles were 1.8-fold higher (p < 0.0005) at 20 weeks and 6.4-fold higher (p < 0.0001) at 35 weeks in the Bio compared to age-matched control F1B hamsters (F1B). The Bio ET-1 levels in the lungs exhibited an only 1.3-fold elevation at 35 weeks. Immunohistochemistry demonstrated the localization of ET-1 mainly in the cardiac myocytes. The treatment with T0201 significantly reduced the heart weight/body weight ratio in the Bio, but did not affect the heart weight/body weight ratio in the F1B. Histologically, T0201 reduced the myocyte diameter of Bio to a level similar with that of F1B. However, T0201 did not affect the extent of fibrosis in Bio or F1B.
Conclusions:
The ET-1 level in the heart of cardiomyopathic hamsters increases in stage-dependent and organ-specific manners. Though myocyte degeneration and subsequent replacement fibrosis do not require an ET-1 pathway, the accelerated synthesis of ET-1 in the heart may contribute to the pathological growth of remaining myocytes in this animal model.
