| Project/Area Number |
15591480
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
KAWASUJI Michio Kumamoto University, Graduate School of Medical Sciences, Department of Cardiovascular Surgery, Professor, 大学院・医学薬学研究部, 教授 (40135067)
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| Co-Investigator(Kenkyū-buntansha) |
KUNITOMO Ryuji Kumamoto University, Graduate School of Medical Sciences, Department of Cardiovascular Surgery, Assistant Professor, 大学院・医学薬学研究部, 講師 (30305015)
SAKAGUCHI Hisashi Kumamoto University Hospital, Department of Cardiovascular Surgery, Lecturer, 医学部附属病院, 助手 (70346980)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | angiogenesis / basic fibroblast growth factor / myocardial ischemia / therapeutic angiogenesis / 血管新生因子 |
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| Research Abstract |
Standard therapies of myocardial revascularization for ischemic heart disease, coronary artery bypass grafting and percutaneous coronary intervention, are often limited because of diffuse coronary lesions or small-caliber vessels, those have a significant impact on a patient's quality of life. The purpose of this study is to develop a novel angiogenic therapy to biologically induce myocardial revascularization using angiogenic growth factors and endothelial progenitor cells. We evaluated the effects of basic fibroblast growth factor(bFGF) on neoangiogenesis, cardiomyocyte apoptosis, myocardial fibrosis, ventricular remodeling and cardiac function in a rat infarction model. Myocardial infarction was induced in rats by ligation of the left anterior descending coronary artery. Rats received intramyocardial injection of saline alone(control), 20 μg of bFGF, or 20 μg of bFGF incorporated into gelatin gel(bFGF+gel). Ventricular function and geometry was evaluated by echography at 2 and 4 wee
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ks. Morphometric study was performed 2 or 4 weeks after treatment using Sirius red stainand a computerized colored-image analysis system. Histological study was performed using von Willebrand factor stain, α smooth muscle actin stain, and TUNEL stain. Capillary density in the infarct border zone was significantly higher in the bFGF and bFGF+gel groups than the control group at 4 weeks. Arteriolar density was significantly higher in the bFGF+gel group at 2 and 4 weeks. Apoptotic cardiomyocytes were significantly fewer in the bFGF and bFGF-i-gel groups. The bFGF+gel group had significantly thicker and less expanded infarcts and showed a better fractional shortening. No difference was found in collagen density of fibrosis between the three groups. Sustained release of bFGF incorporating in gelatin hydrogels enhanced the effects of bFGF on neoangiogenesis, apoptosis and ventricular remodeling after myocardial infraction. We began to investigate the angiogenic effect of endothelial progenitor cells. A clinical study of angiogenic therapy using bFGF protein is in progress. Less
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