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Targeting Calpain for Heart Failure Therapy: Implications From Multiple Murine Models.
Yihui Wang1,2, Biyi Chen2,3, Chun-Kai Huang1,2
1Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
JACC. Basic to Translational Science
|September 4, 2018
Summary
Inhibition of calpain activity protects against heart failure by preventing cardiac remodeling and dysfunction. This study provides evidence for calpain inhibitors as a promising therapeutic strategy for heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Heart failure is a significant cause of death globally, necessitating novel treatments.
- Calpain, a calcium-dependent protease, plays a role in cardiac function and disease.
- Currently, no calpain-targeting drugs are in clinical trials for heart failure.
Purpose of the Study:
- To investigate the therapeutic potential of inhibiting calpain activity in heart failure.
- To evaluate the effects of calpain inhibition on cardiac remodeling and function.
Main Methods:
- Utilized multiple rodent models of heart failure.
- Assessed the impact of calpain inhibition on cardiac ultrastructure and function.
Main Results:
- Calpain inhibition demonstrated protective effects against adverse cardiac remodeling.
- Cardiac function was improved in heart failure models treated with calpain inhibitors.
Conclusions:
- Inhibiting calpain activity is a promising therapeutic strategy for heart failure.
- Targeting calpain may offer a novel mechanism-based treatment for heart failure patients.
Keywords:
CAPN1-OE, calpain-1 overexpressingE-C coupling, excitation-contraction couplingEF, ejection fractionIP, intraperitoneallyISO, isoproterenolJP2, junctophilin-2JP2-OE, junctophilin-2 overexpressingLV, left ventricle/ventricularMI, myocardial infarctionRV, right ventricularSR, sarcoplasmic reticulumT-tubule, transverse tubuleT-tubulesTAB, transverse aortic bandingTTpower, strength of regularity of the T-tubule systemWT, wild-typecalciumcalpainexcitation-contraction couplingheart failure
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