PPARα activation alleviates damage to the cytoskeleton during acute myocardial ischemia/reperfusion in rats

Area of Science:

• Cardiovascular Biology
• Cellular Stress Response
• Molecular Pharmacology

Background:

• The cytoskeleton is crucial for cellular structure and function, and is degraded by calpain during myocardial ischemia/reperfusion injury (MIRI).
• Endoplasmic reticulum (ER) stress may activate calpain during MIRI.
• Peroxisome proliferator-activated receptor α (PPARα) activation can mitigate ischemia/reperfusion damage by modulating stress responses.

Purpose of the Study:

• To investigate whether PPARα activation protects against MIRI-induced cytoskeletal degradation.
• To elucidate the underlying mechanisms of PPARα's protective effects in MIRI.

Main Methods:

• Wistar rats were pretreated with fenofibrate (a PPARα activator) or vehicle before undergoing induced myocardial ischemia/reperfusion.
• Assessed calpain activity, PPARα expression, desmin levels, ER stress markers, cardiac function (ECG, hemodynamic parameters), and cardiomyocyte ultrastructure.

Main Results:

• Ischemia/reperfusion induced significant cytoskeletal damage and cardiac dysfunction.
• PPARα activation by fenofibrate improved cardiac function and reduced cytoskeletal damage.
• Fenofibrate pretreatment decreased ER stress and calpain activity in the heart tissue post-I/R.

Conclusions:

• PPARα activation exerts a protective effect against myocardial ischemia/reperfusion injury.
• This protection is, at least partly, mediated by the inhibition of endoplasmic reticulum stress.
• Inhibiting ER stress represents a potential therapeutic target for protecting the ischemic/reperfused myocardium.