2002 Fiscal Year Final Research Report Summary
Gene therapy and cell transplantation for heart failure.
| Project/Area Number |
12470149
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
COMURO Issei Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (30260483)
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| Co-Investigator(Kenkyū-buntansha) |
HIROI Yukio Tokyo University, University Hospital, Assistant, 医学部付属病院, 助手 (30311624)
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| Project Period (FY) |
2000 – 2002
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| Keywords | LIF / myocardial infarction / plasmid / cardiac remodeling / VEGF / GFP / skeletal muscle / coculture |
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| Research Abstract |
The interleukin 6 (IL-6) family cytokines, including IL-6, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1 have a variety of biological functions not only in the hematopoietic and immune systems but also in other organs including the nervous and cardiovascular systems. In the heart, gp130, the common receptor of IL-6 family, is abundantly expressed and has been reported to be critically involved in the growth and survival of cardiomyocytes. It has been also reported that LIF receptor is abundantly expressed in cardiomyocytes and that LIF induces marked cardiomyocyte hypertrophy. All these findings suggest that LIF may promote survival of cardiomyocytes and regeneration of myocardium. We thus examined the potential usefulness of LIF to treat myocardial infarction (MI). 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 levels. Two weeks later, left ventricular remodeling such as infarct extent and myocardial fibrosis was markedly attenuated in the LIF cDNA-injected mice compared to vehicle-injected ones. More myocardium was preserved and cardiac function was better in the LIF-treated mice than vehicle-injected ones. 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 ceils to the heart and their differentiation into cardiomyocytes. The intramuscular injection of LIF cDNA may induce regeneration of myocardium and provide a novel treatment of MI.
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