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

[Display omitted] •To study the role of CTGF in post-MI cardiac repair and LV remodeling, we antagonized the function of CTGF with a mAb.•Treatment of mice with CTGF mAb during post-MI cardiac repair improved survival and resulted in better preserved LV systolic function.•Treatment with CTGF mAb during post-MI LV remodeling reduced the heart weight to body weight ratio, LV mass, cardiomyocyte hypertrophy, and fibrosis in the remote nonischemic myocardium.•CTGF mAb treatment induced c-Jun N-terminal kinase phosphorylation in ischemic hearts in vivo and in cultured human cardiac fibroblasts.•In conclusion, treatment of mice with CTGF mAb in a model of MI enhances cardiac repair and reduces adverse post-MI LV remodeling. Myocardial infarction (MI)−induced cardiac fibrosis attenuates cardiac contractile function, and predisposes to arrhythmias and sudden cardiac death. Expression of connective tissue growth factor (CTGF) is elevated in affected organs in virtually every fibrotic disorder and in the diseased human myocardium. Mice were subjected to treatment with a CTGF monoclonal antibody (mAb) during infarct repair, post-MI left ventricular (LV) remodeling, or acute ischemia−reperfusion injury. CTGF mAb therapy during infarct repair improved survival and reduced LV dysfunction, and reduced post-MI LV hypertrophy and fibrosis. Mechanistically, CTGF mAb therapy induced expression of cardiac developmental and/or repair genes and attenuated expression of inflammatory and/or fibrotic genes.