Cardiomyocyte apoptosis is associated with increased wall stress in chronic failing left ventricle

Area of Science:

• Cardiology
• Molecular Biology
• Pathophysiology

Background:

• Chronic heart failure (HF) is a complex condition with significant cardiomyocyte loss.
• The mechanisms driving cardiomyocyte apoptosis in HF are not fully understood.
• Elevated cardiac wall stress is a hallmark of HF and may contribute to cell death.

Purpose of the Study:

• To investigate cardiomyocyte apoptosis in a sheep model of chronic heart failure (HF).
• To explore the potential association between elevated cardiac wall stress and cardiomyocyte apoptosis.
• To identify key molecular pathways involved in this process.

Main Methods:

• A sheep model of chronic HF was established using sequential coronary microembolization.
• Western blotting was used to assess the expression of apoptosis-related proteins (Fas, FasL, caspase-8, p20).
• TUNEL assays quantified apoptotic cardiomyocytes, and hemodynamic analysis measured left ventricular (LV) wall stress.

Main Results:

• HF sheep exhibited increased expression of Fas, FasL, and caspase-8, indicating cardiomyocyte apoptosis.
• Apoptotic cardiomyocytes constituted 0.3% of the total, confirmed by TUNEL assays.
• Increased LV wall stress, correlated with Fas/FasL expression, was observed in dilated ventricles.

Conclusions:

• Cardiomyocyte apoptosis is present in chronic HF and is associated with increased cardiac wall stress.
• Elevated wall stress may initiate apoptosis via the Fas/FasL and caspase-8 pathway at intercalated discs.