PP.31.10] ENDOTHELIAL CELL GROWTH SUPPLEMENT IMPROVES CARDIAC FUNCTION FOLLOWING MOUSE MYOCARDIAL INFARCTION

Abstract

Objective: Myocardial infarction (MI) and subsequent heart failure is a leading cause of death in high or middle income countries. Development of treatments that stimulate heart tissue regeneration and revascularization/angiogenesis is important to improve the prognosis of these patients. Our recent work demonstrated that endothelial cell growth supplement (ECGS)-containing medium stimulates endothelial differentiation of c-kit positive cardiac progenitor cells in vitro. The objective of the current work was to test whether ECGS can activate endogenous cardiac progenitor cells and improve cardiac function in a mouse MI model. Design and method: Ligation of the left anterior descending (LAD) artery was performed on mice at 2 months of age under anesthetization and intubation. After displacing the pericardium, a 7–0 silk suture was passed under the LAD artery 2 mm below the left atrium and permanently tied, to eliminate blood flow to the area distal to the suture. ECGS or saline (as control) were injected intramyocardially to the ligation area through a sterile Hamilton syringe with a 30 gauge needle immediately after the ligation. Mice that survived the procedure were maintained for 3 weeks. Echocardiography was performed to monitor the cardiac function prior to organ collection. Results: The results showed that MI increased c-kit positive cells and blood vessel formation as well as massive fibrosis in the infarcted area 3 weeks post-surgery. ECGS treatment significantly reduced cardiac fibrosis, especially in the non-infarcted area and border zone (1.96 ± 0.28 % in ECGS treated group vs 4.54 ± 1.08 % in saline treated control group, p < 0.05). ECGS also improved ejection fraction in these animals compared to the saline treated control group (49.9 ± 2.9 % ECGS treated vs 37.4 ± 4.6 % saline treated, p < 0.05). However, ECGS had no significant effect on infarct size in these animals. Conclusions: The current study demonstrates a reduction in cardiac fibrosis and improvement of cardiac function with ECGS in a mouse MI model, which may link to our in vitro observation that ECGS can activate endothelial differentiation of cardiac progenitor cells.