Cathepsin K-deficiency impairs mouse cardiac function after myocardial infarction

Area of Science:

• Cardiovascular Biology
• Enzymology
• Pathology

Background:

• Extracellular matrix metabolism and cardiac cell death are central to myocardial infarction (MI) pathogenesis.
• Collagenolytic cathepsin K (CatK) is investigated for its role in post-MI left ventricular remodeling.

Purpose of the Study:

• To determine the role of CatK in cardiac function and remodeling following myocardial infarction.
• To investigate the impact of CatK deficiency on the progression of post-MI cardiac dysfunction.

Main Methods:

• Measured plasma CatK levels in patients with acute MI, stable angina, and no coronary heart disease.
• Assessed cardiac function and histological changes in CatK-deficient (Ctsk-/-) and wild-type (Ctsk+/+) mice post-MI.
• Utilized immunofluorescence and biochemical assays to analyze CatK expression, collagen fragments, fibrosis, and cell death/proliferation.

Main Results:

• Elevated plasma CatK levels in acute MI patients compared to controls.
• CatK-deficient mice exhibited worsened cardiac function, increased myocardial fibrosis, and elevated cardiomyocyte death at 7 and 28 days post-MI.
• CatK deficiency was associated with reduced cardiac cell proliferation and increased expression of fibrosis markers.

Conclusions:

• Plasma CatK levels are increased in patients with MI.
• CatK deficiency exacerbates cardiac dysfunction post-MI, highlighting its protective role in mitigating fibrosis and cardiomyocyte death.
• CatK may be a potential therapeutic target for managing adverse cardiac remodeling after MI.