Exogenous HGF Prevents Cardiomyocytes from Apoptosis after Hypoxia via Up-Regulating Cell Autophagy

Area of Science:

• Cardiovascular Biology
• Cellular Mechanisms
• Regenerative Medicine

Background:

• Hepatocyte growth factor (HGF) is recognized for its cardioprotective effects in ischemia, but the underlying cellular mechanisms are not fully understood.
• Autophagy, a cellular degradation process, plays a protective role in the myocardium during early stages of hypoxia.
• This study investigates the interplay between HGF's protective effects and autophagy in cardiomyocytes.

Purpose of the Study:

• To elucidate the association between HGF administration and autophagy in the context of hypoxic cardiomyocytes.
• To determine if HGF-mediated protection against apoptosis in hypoxic cardiomyocytes involves the modulation of autophagy.
• To explore the role of Parkin and mitochondrial autophagy in HGF-induced cardioprotection.

Main Methods:

• Isolation of neonatal rat ventricular myocytes (NRVMs).
• Assessment of cardiomyocyte apoptosis using Hoechst staining and flow cytometry.
• Evaluation of autophagy via transmission electron microscopy and mRFP-GFP-LC3 adenovirus.
• Measurement of mitochondrial membrane potential with JC-1 staining and protein quantification via Western blotting and ELISA.

Main Results:

• Hypoxia induced autophagy in NRVMs, correlating with endogenous HGF release.
• Exogenous HGF administration enhanced autophagy and reduced apoptosis, while HGF neutralization had opposing effects.
• Inhibition of autophagy exacerbated myocyte apoptosis.
• HGF treatment upregulated Parkin, indicating enhanced mitophagy (mitochondrial autophagy) and clearance of damaged mitochondria.

Conclusions:

• Exogenous HGF protects cardiomyocytes from hypoxia-induced apoptosis through a mechanism involving the upregulation of autophagy.
• HGF-induced Parkin expression and subsequent mitophagy represent a potential therapeutic strategy for protecting myocytes during ischemic events.