Abstract 19211: Myocardial Connective Tissue Growth Factor (CCN2/CTGF) Improves Infarct Healing and Attenuates Left Ventricular Remodeling after Myocardial Infarction

Purpose: Myocardial CCN2/CTGF is induced in both experimental and human heart failure. However, its pathophysiological role in ischemic heart failure remains unresolved. Methods: Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were compared with nontransgenic littermate control mice (NLC). Myocardial infarction (MI) was induced by ligation of the left coronary artery in Tg-CTGF (n=22) and NLC mice (n=21). Left ventricular (LV) remodeling and cardiac function was assessed after 4 weeks. Area at risk was estimated in separate groups of animals after perfusion with Evans blue dye, and was similar among Tg-CTGF and NLC mice. In addition, serum levels of CTGF (s-CTGF) were measured in 42 patients admitted to hospital for ST-elevation MI, 2 days, 1 week, 2 months and 1 year after percutaneous coronary intervention (PCI). Cardiac MRI was performed at the same time points to determine infarct size and LV ejection fraction (EF). Results: During the 4 weeks follow-up, survival was significantly higher in Tg-CTGF than in NLC mice; 64% vs. 38%, p Conclusion: CTGF prevents development of ischemic heart failure in mice, and increase in s-CTGF levels in patients after MI is associated with attenuated LV remodeling and improved cardiac function. These results indicate cardioprotective effects of CTGF in ischemic heart failure.