High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice

Area of Science:

• Cardiovascular Medicine
• Metabolic Research
• Biochemistry

Background:

• Protecting the heart post-acute coronary syndrome (ACS) is crucial for recovery and preventing heart failure.
• Targeting cardiac glucose metabolism during early ischemia/reperfusion is vital for myocyte survival.
• High-density lipoprotein (HDL) is known to modulate glucose metabolism in skeletal muscle.

Purpose of the Study:

• To investigate the therapeutic potential of reconstituted HDL (rHDL) in improving cardiac outcomes after myocardial ischemia.
• To determine if rHDL administration post-ischemia enhances cardiac glucose uptake and reduces infarct size.
• To elucidate the direct effects of HDL on cardiomyocyte metabolism and signaling pathways.

Main Methods:

• Administration of a single dose of rHDL in a mouse model of myocardial ischemia.
• Assessment of cardiac glucose uptake, infarct size, and cardiac remodeling.
• Evaluation of cardiomyocyte glucose uptake, glycolysis, and oxidation via the Akt signaling pathway.

Main Results:

• Single-dose rHDL administration post-myocardial ischemia significantly increased cardiac glucose uptake.
• rHDL treatment reduced infarct size and improved cardiac remodeling, leading to enhanced functional recovery.
• These benefits were observed in both metabolically normal and insulin-resistant mice.
• HDL directly enhanced cardiomyocyte glucose uptake, glycolysis, and oxidation through the Akt pathway within 15 minutes of reperfusion.

Conclusions:

• Reconstituted HDL (rHDL) demonstrates significant cardioprotective effects after myocardial ischemia.
• rHDL improves cardiac function and remodeling by enhancing glucose metabolism and activating the Akt pathway.
• Infusible HDL preparations represent a promising therapeutic strategy for managing acute coronary syndromes, particularly in conjunction with percutaneous interventions.