Leukemia Inhibitory Factor Enhances Survival of Cardiomyocytes and Induces Regeneration of Myocardium After Myocardial Infarction
Leukemia Inhibitory Factor Enhances Survival of Cardiomyocytes and Induces Regeneration of Myocardium After Myocardial Infarction
复制标题
DOI：
10.1161/01.cir.0000081773.76337.44
复制
发表时间：
2003-08
期刊：
影响因子：
--
通讯作者：
Y. Zou;H. Takano;M. Mizukami;H. Akazawa;Yingjie Qin;H. Toko;Masaya Sakamoto;T. Minamino;T. Nagai;I. Komuro
中科院分区：
文献类型：
--
作者：
Y. Zou;H. Takano;M. Mizukami;H. Akazawa;Yingjie Qin;H. Toko;Masaya Sakamoto;T. Minamino;T. Nagai;I. Komuro
背景：心肌梗死（MI）是许多国家心脏发病和死亡的主要原因；然而，心肌梗死的治疗仍然有限。方法和结果-我们利用白血病抑制因子（LIF） cDNA证明了一种新的治疗MI的基因疗法。我们在诱导心肌梗死后立即将LIF质粒DNA注射到小鼠大腿肌中，肌内注射LIF cDNA导致循环LIF蛋白浓度显著升高。2周后，注射LIF dna的小鼠左心室重构，如梗死范围和心肌纤维化明显减轻。lif处理的小鼠心肌保存较多，心功能较车用小鼠好。注射LIF cDNA不仅可以防止缺血区心肌细胞的死亡，还可以诱导心肌新生血管。此外，LIF cDNA注射增加了处于细胞周期的心肌细胞数量，增强了骨髓细胞向心脏的动员和向心肌细胞的分化。结论肌内注射LIF cDNA可诱导心肌再生，为心肌梗死提供一种新的治疗方法。
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.