Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in...

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Dilated cardiomyopathy (DCM) and heart failure (HF) are associated with reduced corin levels.
• Corin, a cardiac-selective serine protease, regulates natriuretic peptides and fluid balance.
• Experimental corin restoration shows promise in attenuating HF progression.

Purpose of the Study:

• To investigate whether the beneficial effects of corin in HF are dependent on its catalytic activity.
• To assess the impact of enzymatically inactive corin overexpression in a genetic DCM model.

Main Methods:

• Engineered cardiac overexpression of an enzymatically inactive corin transgene (corin-Tg(i)) in mice.
• Utilized a well-established genetic model of DCM for experimental studies.
• Evaluated survival rates, physiological parameters, cardiac function, and molecular markers.

Main Results:

• Inactive corin (corin-Tg(i)) significantly increased survival in DCM mice compared to controls.
• Reduced pleural effusion, lung edema, and systemic fluid retention were observed with inactive corin.
• Improved cardiac ejection fraction and fractional shortening, with decreased ventricular dilation.
• Decreased plasma levels of atrial natriuretic peptide, cyclic guanosine monophosphate, and neprilysin.
• Increased cardiac phosphorylated glycogen synthase kinase-3β (pSer9-GSK3β) levels.

Conclusions:

• Catalytically inactive corin demonstrates protective effects in experimental DCM.
• The beneficial impact of cardiac corin on HF progression and survival does not require its serine protease activity.
• Inactive corin mitigates fluid retention, enhances cardiac function, and modulates key HF biomarkers.