An eNAMPT-neutralizing mAb reduces post-infarct myocardial fibrosis and left ventricular dysfunction.

Area of Science:

• Cardiovascular Biology
• Immunology
• Pharmacology

Background:

• Myocardial infarction (MI) leads to adverse ventricular remodeling, fibrosis, and heart failure.
• Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is implicated in ventricular remodeling via TLR4 inflammatory pathway activation.

Purpose of the Study:

• To investigate the therapeutic potential of an eNAMPT-specific monoclonal antibody (mAb) in attenuating cardiac inflammation and fibrosis post-MI.
• To assess the efficacy of ALT-100 mAb in a rat model of myocardial infarction.

Main Methods:

• Rats underwent induced myocardial infarction and received ALT-100 mAb or saline treatment.
• Cardiac function was evaluated using echocardiography.
• Myocardial histopathology, including collagen deposition, was assessed.
• ^99mTc-labeled ALT-300 was used for imaging eNAMPT expression.

Main Results:

• ALT-100 mAb treatment significantly improved cardiac function and myocardial histopathology 4 weeks post-MI.
• A significant reduction in collagen volume fraction was observed in the ALT-100 treated group compared to controls.
• ^99mTc-ALT-300 imaging demonstrated eNAMPT expression in the ischemic myocardium, increasing over time.

Conclusions:

• Neutralizing eNAMPT with ALT-100 mAb is a promising therapeutic strategy for myocardial infarction.
• This approach effectively reduces chronic inflammation and fibrosis, preserving cardiac function post-MI.
• Targeting the eNAMPT/TLR4 pathway offers a novel therapeutic avenue for managing heart failure after MI.