Abstract 20699: Neuregulin GGF2 Retains Cardioprotective Effects in the Presence of a High Fat Diet in Post-Myocardial Infarcted Rats
Neuregulins, a cardioprotective factor secreted by coronary endothelium, and the NRG-1β homolog, glial growth factor 2 (GGF2) have been shown to promote recovery of cardiac function after myocardial infarction (MI) in rats. However, the impact of a high-fat diet following MI on the cardioprotective effects of GGF2 has not been reported. In the present study, we evaluated the therapeutic effects of intravenous (IV) GGF2 administration on cardiac function after MI in rats with and without high-fat feeding. MI was induced by ligation of the left anterior descending (LAD) coronary artery. Surviving rats were randomized to receive vehicle (n=10), 0.5 mg/kg GGF2 (low dose) (n= 9), or 2.6 mg/kg GGF2 (high dose) (n=9) in the presence or absence of high-fat diet starting from post-MI day 7 through 38. Residual left ventricular (LV) post-MI function and morphology were examined by echocardiography. Post-MI and post-treatment cardiac collagen deposition, oxidative stress (formation of protein carbonyls) and proteomic changes (by two-dimensional difference gel electrophoresis and mass spectrometry) were also examined. Fractional shortening (FS) values were significantly greater (p<0.05) in both of the GGF2 treatment groups than in the vehicle-treated MI group at the end of study, indicating improved LV contractility and function. High-fat feeding did not impair the cardioprotective effects of GGF2 at either dose. Cardiac collagen deposition in the LV remote from the infarct was significantly increased in vehicle-treated MI versus sham rats (p<0.05); however, no difference in cardiac fibrosis was observed in GGF2-treated MI rats at both doses vs. vehicle-treated MI rats (p>0.05). In-depth mining of the post-MI myocardial proteome revealed 15 proteins that were altered in abundance by low dose GGF2 treatment vs. vehicle-treatment, including cytoskeletal, energy metabolic, and cardioprotective proteins. Myocardial protein carbonyls were increased in the vehicle-treated vs. sham MI rats. Low dose GGF2 treatment decreased myocardial protein carbonyls in post-MI rats. These findings support the use of GGF2 to restore ventricular function after MI and suggest that GGF2 may have prophylactic utility against heart failure following MI.
- © 2010 by American Heart Association, Inc.