Protease corin expression and activity in failing hearts

Area of Science:

• Cardiology
• Biochemistry
• Molecular Biology

Background:

• Atrial and brain natriuretic peptides (ANP and BNP) are crucial for blood pressure and cardiac regulation.
• Elevated precursor forms (pro-ANP, pro-BNP) in heart failure (HF) suggest impaired natriuretic peptide processing.
• The mechanism behind this processing deficiency in HF remains unclear.

Purpose of the Study:

• To investigate corin protease expression and activity in failing mouse and human hearts.
• To determine if altered corin levels or activity contribute to natriuretic peptide deficiency in heart failure.

Main Methods:

• Western blotting and ELISA to quantify corin protein levels in mouse and human heart tissues.
• Fluorogenic substrate and pro-ANP processing assays to measure corin catalytic and biological activity.
• Comparison of corin in nonfailing, hypertrophic, and failing hearts.

Main Results:

• Corin protein levels increased in failing mouse hearts and human ventricular tissue.
• Corin activity, however, did not increase in failing hearts, remaining unchanged.
• This dissociation suggests a problem with corin activation rather than expression.

Conclusions:

• Corin activation is a rate-limiting step in the context of failing hearts.
• Insufficient corin activation impairs natriuretic peptide processing in HF.
• This may contribute to fluid retention and cardiac dysfunction in heart failure patients.