Endothelin-3 induces hypertrophy of cardiomyocytes by the endogenous endothelin-1-mediated mechanism
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Summary
This summary is machine-generated.Endothelin-3 (ET-3) causes cardiac hypertrophy in cardiomyocytes by increasing cell size and protein synthesis. This effect is mediated by endogenous endothelin-1 (ET-1), acting as an autocrine/paracrine factor through ETB and ETA receptors.
Area Of Science
- Cardiovascular Biology
- Molecular Cardiology
- Endocrinology
Background
- Endothelin-1 (ET-1) is known to mediate angiotensin II-induced cardiomyocyte hypertrophy.
- The role of endothelin-3 (ET-3) in cardiomyocyte hypertrophy requires further investigation.
Purpose Of The Study
- To investigate whether endothelin-3 (ET-3) induces hypertrophy in cultured neonatal rat cardiomyocytes.
- To determine if endogenous endothelin-1 (ET-1) mediates ET-3-induced cardiac hypertrophy.
Main Methods
- Primary culture of neonatal rat cardiomyocytes.
- Measurement of cell surface area and protein synthesis ([3H]leucine incorporation).
- Northern blot analysis for skeletal alpha-actin mRNA levels.
- Use of ETB receptor antagonist (BQ788), ETA receptor antagonist (BQ123), and antisense oligonucleotides against preproET-1 mRNA.
Main Results
- ET-3 (10(-7) M) increased cardiomyocyte surface area after 48 hours.
- ET-3 dose-dependently stimulated protein synthesis and skeletal alpha-actin mRNA expression.
- ET-3 also increased endogenous ET-1 mRNA and immunoreactive ET-1 release.
- Both ETB and ETA receptor antagonists, as well as ET-1 antisense oligonucleotides, inhibited ET-3 effects.
Conclusions
- Endothelin-3 (ET-3) induces cardiac hypertrophy in cardiomyocytes.
- Endogenous endothelin-1 (ET-1) plays a crucial autocrine/paracrine role in mediating ET-3-induced cardiomyocyte hypertrophy.
- The effects of ET-3 are mediated via both ETB and ETA receptors, involving the local production of ET-1.