Published Online
on July 14, 2003

A more recent version of this article appeared on August 12, 2003

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Submitted on January 30, 2003
Revised on April 14, 2003
Accepted on April 16, 2003

Leukemia Inhibitory Factor Enhances Survival of Cardiomyocytes and Induces Regeneration of Myocardium After Myocardial Infarction

Yunzeng Zou MD, PhD, Hiroyuki Takano MD, PhD, Miho Mizukami MD, Hiroshi Akazawa MD, Yingjie Qin MD, Haruhiro Toko MD, Masaya Sakamoto MD, Tohru Minamino MD, PhD, Toshio Nagai MD, PhD, and Issei Komuro MD, PhD^*

From the Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

^* To whom correspondence should be addressed. E-mail: komuro-tky{at}umin.ac.jp.

Background--Myocardial infarction (MI) is a leading cause of cardiac morbidity and mortality in many countries; however, the treatment of MI is still limited.

Methods and 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.

Key words: gene therapy • muscles • leukemia inhibitory factor • myocardial infarction • regeneration

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