Regulation of Cardiac Regeneration by ACE Inhibition Following Donor Heart Myocardial Infarction After Heterotopic Transplantation in Tg Mice

BACKGROUND: Experimental and clinical evidence have recently shown that pluripotent stem cells can be mobilized using granulocyte-colony stimulating factor (GCSF) and may enhance myocardial regeneration after acute myocardial infarction (MI). The present study investigated the pharmacological role of angiotensin-converting enzyme inhibition on cardiac regeneration after MI using a mouse model of heterotopic cardiac transplantation and coronary ligation. METHODS AND RESULTS: Isogenic heterotopic cardiac transplantations and simultaneous coronary ligations were performed in green fluorescent protein (GFP) mice to produce MI in the donor heart. Five mice in the ligation group were treated with oral perindopril (PE) after the operation. Three mice in the ligation group were treated with subcutaneous GCSF and 4 angiotensin II type1a receptor knockout (AT1aRKO) mice were used as well. At 60 days after the operation, the maximum GFP-positive cell counts in the GCSF group were significantly higher than in the other 4 groups. The maximum GFP-positive cell counts in both the AT1aRKO and ligation & PE groups were significantly higher than in the sham and ligation groups. CONCLUSIONS: Pharmacological modification for cardiac regeneration may provide an alternative treatment for subsequent cardiac remodeling in the late phase of MI.