Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction

Area of Science:

• Cardiovascular Research
• Fibrosis Biology
• Immunotherapy

Background:

• Myocardial infarction (MI) leads to cardiac fibrosis, impairing heart function and increasing arrhythmia risk.
• Connective tissue growth factor (CTGF) is upregulated in fibrotic conditions, including diseased human hearts.

Purpose of the Study:

• To investigate the therapeutic potential of a CTGF monoclonal antibody (mAb) in mitigating adverse cardiac remodeling after myocardial infarction.
• To elucidate the mechanisms by which CTGF mAb therapy impacts cardiac gene expression and fibrotic processes.

Main Methods:

• Mice models were used to assess CTGF mAb treatment during infarct repair, post-MI remodeling, and acute ischemia-reperfusion injury.
• Evaluated effects on survival, left ventricular (LV) function, hypertrophy, fibrosis, and gene expression profiles.

Main Results:

• CTGF mAb therapy during infarct repair significantly improved survival rates in mice.
• Treatment reduced LV dysfunction, hypertrophy, and cardiac fibrosis following myocardial infarction.
• Mechanistically, CTGF mAb induced cardiac developmental/repair genes and suppressed inflammatory/fibrotic genes.

Conclusions:

• Targeting CTGF with a monoclonal antibody represents a promising therapeutic strategy for reducing cardiac fibrosis and dysfunction post-MI.
• CTGF inhibition offers a novel approach to promote cardiac repair and prevent adverse remodeling after heart injury.