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Published on: September 18, 2017
Dynamin-2 mediates heart failure by modulating Ca2+ -dependent cardiomyocyte apoptosis
Jun Li1, Da-Sheng Zhang, Jiang-Chuan Ye
1Key Laboratory of Basic Research in Cardiology of Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200120, China.
International Journal of Cardiology
|February 16, 2013
Summary
Dynamin-2 (DNM2) is crucial for maintaining heart function. Reduced DNM2 levels in heart failure (HF) lead to cardiomyocyte apoptosis and disease progression, suggesting DNM2 as a potential therapeutic target for HF.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Heart failure (HF) is a growing epidemic with significant healthcare and societal impact.
- Cardiomyocyte membrane remodeling is implicated in HF pathogenesis.
- The role of dynamin (DNM), a key membrane-remodeling GTPase, in HF remains largely unknown.
Purpose of the Study:
- To investigate the association between dynamin (DNM) and heart failure (HF).
- To elucidate the role of dynamin-2 (DNM2) in cardiac function and HF development.
Main Methods:
- Utilized experimental animal models of HF and human failing heart tissue.
- Generated DNM2-deficient zebrafish to assess cardiac function.
- Conducted mechanistic studies to explore the molecular pathways affected by DNM2 deficiency.
Main Results:
- DNM2 protein levels decrease progressively with HF progression in animal models and human hearts.
- DNM2 deficiency in zebrafish leads to cardiac apoptosis and severe HF.
- DNM2 downregulation results in cardiomyocyte calcium overload, mitochondrial apoptosis, and enhanced L-type Ca(2+) channel translocation due to membrane trafficking defects.
Conclusions:
- DNM2 plays a critical role in mediating heart failure by regulating calcium-dependent cardiomyocyte apoptosis.
- Modulating DNM2 function presents a potential novel therapeutic strategy for treating heart failure.
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