| Co-Investigator(Kenkyū-buntansha) |
FUJII Satoshi Hokkaido Univ., Medical, Hospital, Lec., 医学部・附属病院, 講師 (90291228)
OKAMOTO Hiroshi Hokkaido Univ., Medical, Hospital, Lec., 医学部・附属病院, 講師 (50260394)
UEDE Toshimitsu Hokkaido Univ., Institut.for Genetic Med., Prof., 遺伝子病制御研究所, 教授 (00160185)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2000: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Research Abstract |
The objectives of this research project were 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 demonstrated that gene expression and venule capillary densities of VEGF recovered with that in dilated cardiomyopathy model hamster, the myocardial cell density decreases for a heart failure stage, and that the capillary density decreases, while the fibrillation organization volume increases, and that it suppresses the gene expression of VEGF concomitantly that suppression of the myocardial fibrosis. It was planned that 1999 fiscal year, we introduced human angiopoietin 1 and 2 genes to the heart muscle with VEGF as a target gene. Until now, there was a problem that adenovirus, which was recognized as a foreign body. In order to inhibit costimulatory signal of T cells, AdexCTLA4Ig was developped, and the technique which induced the immunologic tolerance was induced by AdexCTLA4Ig. AdexCTLA4Ig has already 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 gene transfection can be done and it uses are being tried 2 each. Moreover, 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 there remain several steps to be overcome before making decision, these sophisticated studies provide original and important findings in the field of molecular cardiology.
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