Leukemia inhibitory factor enhances survival of cardiomyocytes and induces regeneration of myocardium after myocardial infarction.
BACKGROUND
Myocardial infarction (MI) is a leading cause of cardiac morbidity and mortality in many countries; however, the treatment of MI is still limited.


RESULTS
We demonstrate a novel gene therapy for MI using leukemia inhibitory factor (LIF) cDNA. We injected LIF plasmid DNA into the thigh muscle of mice immediately after inducing MI. Intramuscular injection of LIF cDNA resulted in a marked increase in circulating LIF protein concentrations. Two weeks later, left ventricular remodeling, such as infarct extent and myocardial fibrosis, was markedly attenuated in the LIF cDNA-injected mice compared with vehicle-injected mice. More myocardium was preserved and cardiac function was better in the LIF-treated mice than in the vehicle-injected mice. Injection of LIF cDNA not only prevented the death of cardiomyocytes in the ischemic area but also induced neovascularization in the myocardium. Furthermore, LIF cDNA injection increased the number of cardiomyocytes in cell cycle and enhanced mobilization of bone marrow cells to the heart and their differentiation into cardiomyocytes.


CONCLUSIONS
The intramuscular injection of LIF cDNA may induce regeneration of myocardium and provide a novel treatment for MI.
Zou
Yunzeng
Y
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Takano
Hiroyuki
H
Mizukami
Miho
M
Akazawa
Hiroshi
H
Qin
Yingjie
Y
Toko
Haruhiro
H
Sakamoto
Masaya
M
Minamino
Tohru
T
Nagai
Toshio
T
Komuro
Issei
I
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006334:Heart Function Tests / Q000187:drug effects; D007273:Injections, Intramuscular; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
D018076:DNA, Complementary; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines