Plasma cathepsin D isoforms and their active metabolites increase after myocardial infarction and contribute to...

Area of Science:

• Cardiovascular Biology
• Enzymology
• Biochemistry

Background:

• Plasma renin activity (PRA) often increases post-myocardial infarction (MI), potentially contributing to adverse cardiac remodeling via elevated angiotensin II.
• The study investigates the role of cathepsin D, an enzyme with sequence homology to renin, in the context of MI.

Purpose of the Study:

• To determine if myocardial infarction (MI) leads to cardiac release of cathepsin D.
• To assess whether cathepsin D contributes to angiotensin formation post-MI.
• To evaluate the impact of cathepsin D on clinical plasma renin activity (PRA) assays.

Main Methods:

• Analysis of circulating renin and cathepsin D in plasma from control and MI patients (7-20 hours post-MI).
• Utilized shallow gradient focusing for independent enzyme measurement.
• Assessed the effect of adding cathepsin D to control plasma on PRA using a clinical assay.

Main Results:

• Cathepsin D levels were significantly elevated in MI patient plasma (P < 0.001).
• Circulating active cathepsin D metabolites were also significantly increased post-MI (P < 0.04) and comprised the majority of plasma cathepsin D activity.
• Addition of cathepsin D to control plasma significantly increased measured PRA (P = 0.005).

Conclusions:

• Plasma cathepsin D is significantly elevated 7-20 hours after MI, primarily as active metabolites.
• Circulating cathepsin D can lead to falsely elevated clinical PRA measurements.
• Cathepsin D may represent an alternative enzymatic pathway for angiotensin formation following MI.