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<0.05. In vivo pressure-volume analysis after 4 weeks revealed preserved cardiac performance in Tg-CTGF mice, as measured by dp/dt max, LV end-diastolic and end-systolic pressures, and cardiac output. End-point analysis after excision of the hearts revealed attenuation of cardiac hypertrophy in Tg-CTGF vs NLC mice (Heart weight/body weight ratio; 5.3±0.2mg/g, n=14 vs 8.0±0.9mg/g, n=9, p<0.05). Also, markers of myocardial remodeling, i.e. myocardial BNP and beta-myosin heavy chain mRNA levels were significantly lower in Tg-CTGF than in NLC hearts. Interestingly, in patients in which s-CTGF levels increased from day 2 after PCI until 2 months after PCI (n=21), infarct healing was significantly improved and LV remodeling attenuated one year after the ischemic event. Consistently, EF was also significantly higher in these patients after one year, as compared to patients with unaltered or decreased s-CTGF levels (n=21).
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.
- © 2010 by American Heart Association, Inc.