Recombinant Soluble Corin Improves Cardiac Function in Mouse Models of Heart Failure

Area of Science:

• Cardiovascular Research
• Protease Function
• Heart Failure Pathophysiology

Background:

• Corin is a transmembrane protease crucial for activating natriuretic peptides (ANP, BNP).
• Dysfunctional corin is linked to heart failure development and progression.
• A soluble form of corin (sCorin) was investigated for therapeutic potential.

Purpose of the Study:

• To characterize soluble corin (sCorin) and its enzymatic activity.
• To evaluate the therapeutic effects of sCorin in mouse models of heart failure.
• To assess sCorin's impact on cardiac morphology, function, and key biomarkers.

Main Methods:

• sCorin was engineered, expressed, purified, and validated for pro-ANP processing.
• Pharmacokinetic studies determined sCorin's plasma half-life in mice.
• Heart failure was induced via coronary artery ligation and transverse aortic constriction.

Main Results:

• Purified sCorin effectively converted pro-ANP to ANP, stimulating cellular cGMP production.
• sCorin exhibited favorable plasma half-lives (3.5-8.3 hours) after administration.
• In heart failure models, sCorin increased ANP/BNP/cGMP, decreased NT-proANP/angiotensin II/aldosterone, reduced cardiac hypertrophy/fibrosis, and improved cardiac function.

Conclusions:

• sCorin enhances natriuretic peptide processing and activity.
• sCorin treatment suppresses the detrimental renin-angiotensin-aldosterone system.
• sCorin demonstrates significant therapeutic benefits for cardiac morphology and function in heart failure.