| Project/Area Number |
14570680
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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 |
Circulatory organs internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
SAKAMOTO Tomohiro Kumamoto University, Hospital, Lecturer, 医学部附属病院, 講師 (00301375)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Michihiro Kumamoto University, Graduate School of Medical Sciences, Associate Professor of Medicine, 大学院・医学薬学研究部, 助教授 (30264295)
OGAWA Hisao Kumamoto University, Graduate School of Medical Sciences, Professor of Medicine, 大学院・医学薬学研究部, 教授 (50177135)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | PAI-1 / adipocytes / free fatty acids / acute coronary syndrome / activated protein C / nicorandil / 冠血流予備能 / プラスミノゲンアクチベーターインヒビター / インスリン抵抗性 / 脂肪酸分画 |
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| Research Abstract |
We investigated coagulation and fibrinolytic activity in patients with acute coronary syndrome(ACS). Type-1 plasminogen activator inhibitor(PAI-1) is known to be the main controller of the fibrinolytic system. PAI-1 is closely related with appearance and disappearance of intracoronary thrombus, and furthermore with prognosis of coronary artery disease. It has been elucidated that PAI-1 is elevated in ACS patients. There were significant relation between the elevation of PAI-1 and visceral fat amount. In other words, PAI-1 was elevated in obese patients. It is well known that adipose tissue is one of the main sources of PAI-1 in plasma. On the other hand, plasma levels of non-esterified fetty acids(NEFA) were elevated in obese subjects. Plasma levels of NEFA were closely related with those of PAI-1 activity. To elucidate which NEFAs affected PAI-1 production from adipose tissue, we investigated the PAI-1 production of cultured mouse adipose tissue(3T3-L1 adipocytes). Of all major NEFAs
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in plasma, NEFAs with unsaturated ponds such as oleic acid and linolenic acid activated PAI-1 production from the cells. As compared with saturated NEFAs.
PAI-1 activity is closely related with prognosis of coronary artery disease and it is important to keep the level lower. We elucidated that intravenous administration of activated protein C(APC) as a conjunctive therapy with thrombolysis in patients with acute myocardial infarction was effective to prevent reocclusion of the recanalized infarct related-coronary artery by thrombolytic therapy. APC inhibits not only factors Va and VIIIa but also PAI-1. In patients with chronic ischemic heart disease, oral administration of nicorandil was also effective to decrease the PAI-1 activity.
The other pharmacological interventions to decrease plasma PAI-1 levels include the inhibition of PAI-1 production of adipocytes by NEFAs. Fibrates which decrease triglycerides' levels and induction of β-oxidation of NEFAs may be possible. Further experimental and clinical examinations are needed. Less
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