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Cloning of hamster preproendothelin-1 cDNA and its expression in the heart
T Miyauchi1, T Kobayashi, R Yamauchi
1Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
Insights
Endothelin-1 (ET-1) plays a key role in heart failure. This study found elevated ET-1 mRNA in failing hamster hearts, suggesting its involvement in the condition.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Heart Failure Pathophysiology
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor with known roles in cardiovascular function.
- Its specific pathophysiologic involvement in heart failure requires further elucidation.
Purpose of the Study:
- To investigate the role of endothelin-1 (ET-1) in the failing heart.
- To clone and sequence hamster preproET-1 cDNA and analyze preproET-1 mRNA expression in a heart failure model.
Main Methods:
- Cloned and sequenced hamster preproET-1 cDNA from CHF146 hamster hearts.
- Utilized 46-week-old CHF146 hamsters and age-matched controls.
- Assessed cardiac function via left ventricular (+ dP/dtmax) and end-diastolic pressure measurements.
- Quantified preproET-1 mRNA expression in the left ventricle using quantitative methods.
Main Results:
- Hamster preproET-1 showed 89% amino acid homology to rat preproET-1.
- Deduced hamster mature ET-1 sequence is identical to human, rat, canine, and mouse ET-1.
- CHF146 hamsters exhibited significantly reduced LV + dP/dtmax and elevated LV end-diastolic pressure, indicating congestive heart failure.
- PreproET-1 mRNA expression was significantly upregulated in the left ventricles of CHF146 hamsters compared to controls.
Conclusions:
- Endogenous endothelin-1 (ET-1) is implicated in the pathophysiology of congestive heart failure in CHF146 hamsters.
- Elevated preproET-1 mRNA expression suggests increased ET-1 production contributes to the failing heart condition.
- Findings support ET-1's role in cardiac hypertrophy and myocyte injury observed in heart failure.
Abstract:
To elucidate the pathophysiologic roles of endothelin-1 (ET-1) in the heart, we first cloned and sequenced a part of hamster preproET-1 cDNA from the heart of the CHF146 hamsters. The amino acid sequence has 89% homology to that of rat preproET-1 in the cloned part. The deduced hamster 21-residue mature ET-1 is identical to human, rat, canine, and mouse ET-1. In the next step we investigated the expression of preproET-1 mRNA in the failing heart of CHF146 hamsters. For this purpose, we used 46-week-old CHF146 hamsters and age-matched control healthy hamsters. Left ventricular (LV) + dP/dtmax was significantly lower in CHF146 hamsters than in control hamsters. LV end-diastolic pressure was significantly higher in CHF146 hamsters than in control hamsters, as was central venous pressure. These results suggested that the CHF146 hamsters developed congestive heart failure. The expression of preproET-1 mRNA was greatly enhanced in the LV of the CHF146 hamsters. Because it has been reported that ET-1 induces cardiac hypertrophy and injury to cardiac myocytes in addition to its potent positive inotropic and chronotropic actions, the present findings suggest that endogenous ET-1 plays pathophysiologic roles in the failing heart of CHF146 hamsters.