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.


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.
Matsushima
Atsushi
A
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Japan.
Nakamura
Hiroshi
H
Umemoto
Seiji
S
Matsuzaki
Masunori
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D016027:Heart Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000188:drug therapy*; D011183:Postoperative Complications / Q000188:drug therapy*; D012038:Regeneration / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D016042:Transplantation, Heterotopic; D020257:Ventricular Remodeling / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D049452:Green Fluorescent Proteins