Overexpression of microRNA-145 protects against rat myocardial infarction through targeting PDCD4

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Biology

Background:

• Myocardial infarction (MI) is a leading cause of mortality worldwide.
• Understanding the molecular mechanisms underlying MI is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of microRNA-145 (miR-145) in myocardial infarction (MI) and hypoxia-induced cardiomyocyte injury.
• To elucidate the underlying molecular mechanisms, including the identification of miR-145 targets.

Main Methods:

• Myocardial infarction was induced in rats via left anterior descending artery ligation.
• Quantitative real-time PCR (qRT-PCR) and Western blot analysis were used to measure gene and protein expression.
• Lentivirus-mediated gene delivery was employed for miR-145 overexpression.
• Cardiomyocyte apoptosis and mitochondrial function were assessed under hypoxia.

Main Results:

• miR-145 levels were significantly decreased in MI rats compared to sham controls.
• Overexpression of miR-145 improved cardiac function, reduced infarct size, and attenuated apoptosis in MI rats.
• Programmed cell death protein 4 (PDCD4) was identified as a direct target of miR-145 in cardiomyocytes.
• PDCD4 overexpression reversed the protective effects of miR-145 against hypoxia-induced apoptosis and mitochondrial dysfunction.

Conclusions:

• The miR-145/PDCD4 axis plays a critical role in the pathophysiology of MI.
• miR-145 exerts cardioprotective effects by inhibiting mitochondria-mediated apoptosis, making it a potential therapeutic target for MI treatment.