A novel myocardial protection with in vivo gene transfection

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To develop a myocardial protection against is chemia-reperfusion injury, many kinds of pharmacological approaches have been tried. But they appear to have limited efficacy even now. Recently, another approach which uses self-preservation systems, such as is chemic preconditioning and heat shock, is expected to develop a further advanced myocardial protection. HSP70 is reported to be induced under various forms of stress such as ischemis, heat shock, or drug administration and enhance myocardial tolerance to ischemia-reperfusion injury. The object of this study is to develop a novel method for myocardial protection with gene transfection through enforcing the self-preservation system, such as HSP70. First, we isolated the role of HSP70 in coronary endothelial cells and in cardiac myocytes under conditions of ischemia-reperfusion injury using in vitro gene transfection. Next, we developed the oprimal method for in vivo gene transfection to whole heart by intracoronary infusion of HVJ-liposome. Then, we demonstrated that it is possible to introduce HSP70 into the entire heart with this gene transfection method and enhance myocardial tolerance to ischemia-reperfusion injury. These results showed the possibility of clinical application of gene therapy (long-term cardiac preservation) with HSP70 to ischemia-reperfusion injury of the heart.