|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1998 : ¥2,500,000 (Direct Cost : ¥2,500,000)
The aim of this research project was to clarify whether it establishes the usefulness of the angiogenesis therapy on the assumption of the mechanism that in remodeling process of the failing myocardium, abnormalities in the capillary microvasculature by the angiogenesis develops in myocardial blood flow and that the cardiac function deteriorates further in the failing heart. It was observed that gene expression and venule capillary density of VEGF recovered with that in dilated cardiomyopathy model hamster, the myocardial cell density decreases for a cardiac insufficiency stage, and that the capillary density decreases, while the fibrillation organization volume increases, and that it suppresses the gene expression of VEGF, that and, it suppresses the myocardial fiber by the pharmacotherapy. It was planned that 1999 fiscal year, we introduced human angiopoietin 1 and 2 genes to the heart muscle with VEGF as a gene as a target. Until now, there was a problem that adenovirus, which was recognized as a foreign body. In order to suppress costimulatory signal of a T cell, AdexCTLA4Ig was produced, and the technique which induced the immunologic tolerance condition was developed. Already Adex CTLA4Ig was made, and the extensive expression of LacZ was confirmed. The endothelial cell is induced the angiogenesis by VEGF, and activating factor angiopoietin 1 and control factor angiopoietin 2 adjust it. At present, VEGF, angiopoietin 1 , angiopoietin 2 single or gene introduction it uses are being tried 2 each. And, microvasculature construction using synchrotron radiation SPring8 with the newborn blood vessel is being analyzed, since to catch the change of the angioarchitecture in the conventional method is difficult. Altough ther remain several steps to be overcome before making decision, these sophisticated studies provide original and important findings in the field of molecular cardiology.