Project/Area Number |
10557071
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Osaka University |
Principal Investigator |
HORI Masatsugu Graduate School of Medicine, Osaka University, Professor, 医学系研究科, 教授 (20124779)
|
Co-Investigator(Kenkyū-buntansha) |
NISHIDA Masashi Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (40283783)
KITAKAZE Masafumi Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (20294069)
KUZUYA Tsunehiko Graduate School of Medicine, Osaka University, Associate Professor, 医学系研究科, 助教授 (80150340)
TOYOFUKU Toshihiko Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手
OHTSU Kin-ya Graduate School of Medicine, Osaka University, Assistant Professor, 医学系研究科, 助手 (20294051)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1999: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1998: ¥7,700,000 (Direct Cost: ¥7,700,000)
|
Keywords | Acute Coronary Syndrome / Oxidative Stress / Mn-SOD / Inflammation / 血管平滑筋細胞 / プレコンディショニング / 温熱負荷 / TNF-α / 細胞障害 |
Research Abstract |
Recent studies revealed that myocardial infarction is not occurred from highly progressive atherosclerotic lesions, but rather from relatively mild lesions. Therefore, prevention of rupture of unstable coronary plaque is necessary for the prevention of acute myocardial infarction. In this study, we examined whether regulation of oxygen radical in vascular smooth muscle cells can modulate stability of atherosclerotic plaque. In the first year, we demonstrated that antioxidative enzyme, Mn-SOS, was induced in cultured vascular smooth muscle cells by the preconditioning with heat shock or TNF-α together with the acquisition of tolerance to oxidative stress. In the second year, we revealed that the induction of Mn-SOD by TNF-α was inhibited by the addition of antisenseoligodeoxyribonucleotide (AODN) to Mn-SOD and that the tolerance to oxidative stress was also abolished by the treatment with AODN. On the other hand, lipofection of Mn-SOD to smooth muscle cells introduced Mn-SOD in mitochondria of cells and augmented tolerance to oxidative stress. These results suggest that the expression of antioxidative enzyme in vascular wall cells is closely related to the survival of smooth muscle cells and that by introducing antioxidative enzyme in cells could stabilize atherosclerotic plaque.
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