The role of fatty acids metabolism in the onset of acute coronary syndrome

脂肪酸代谢在急性冠脉综合征发病中的作用

• 批准号: 14570680
• 负责人: SAKAMOTO Tomohiro
• 金额: $ 1.6万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570680/
• 关键词: 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

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 … More 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

我们研究了急性冠状动脉综合征（ACS）患者的凝血和纤溶活性。 1型纤溶酶原激活剂抑制剂（PAI-1）已知是纤溶系统的主要控制者。 PAI-1与冠脉内血栓的出现和消失密切相关，进而与冠心病的预后密切相关。已阐明 ACS 患者中 PAI-1 升高。 PAI-1升高与内脏脂肪量呈显着相关。换句话说，肥胖患者的 PAI-1 升高。众所周知，脂肪组织是血浆中PAI-1的主要来源之一。另一方面，肥胖受试者的血浆非酯化脂肪酸（NEFA）水平升高。血浆NEFA水平与PAI-1活性密切相关。为了阐明哪些 NEFA 影响脂肪组织中 PAI-1 的产生，我们研究了培养的小鼠脂肪组织（3T3-L1 脂肪细胞）的 PAI-1 产生。在血浆中的所有主要 NEFA 中，具有不饱和池的 NEFA（例如油酸和亚麻酸）可激活细胞中 PAI-1 的产生。与饱和NEFAs相比，PAI-1活性与冠心病的预后密切相关，保持较低水平非常重要。我们阐明，对急性心肌梗死患者静脉注射活化蛋白C（APC）作为溶栓治疗的联合疗法，可有效防止溶栓治疗后再通的梗死相关冠状动脉再闭塞。 APC 不仅抑制因子 Va 和 VIIIa，还抑制 PAI-1。在慢性缺血性心脏病患者中，口服尼可地尔也能有效降低 PAI-1 活性。降低血浆 PAI-1 水平的其他药理学干预措施包括通过 NEFA 抑制脂肪细胞产生 PAI-1。贝特类药物可能会降低甘油三酯水平并诱导 NEFA 的 β 氧化。还需要进一步的实验和临床检查。较少的

项目成果

Effect of nicorandil of endogenous fibrinolytic capacity in patients with coronary artery disease

尼可地尔对冠心病患者内源性纤溶能力的影响

• 发表时间: 2004
• 期刊: Circulation Journal 68(3)
• 作者: Liu;H-W.;Iwai;M.;Takeda-Matsubara;Y.;Wu;L.;Li;J-M.;Okumura;M.;Cui;T-X.;Horiuchi;M.;Sakamoto T
• 通讯作者: Sakamoto T

Plasma thioredoxin levels and platelet aggregability in patients with acute myocardial infarction

急性心肌梗死患者血浆硫氧还蛋白水平和血小板聚集性

• 发表时间: 2003
• 期刊: American Heart Journal 146(3)
• 作者: Miyamoto S

Sakamoto T: "TNT-α and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes"American Journal of Physiology. 276. C1391-C1397 (1999)

Sakamoto T：“TNT-α 和胰岛素单独或协同作用，诱导脂肪细胞中纤溶酶原激活剂抑制剂 1 的表达”《美国生理学杂志》276。C1391-C1397 (1999)。

Plasminogen activator inhibitor contributes to the coronary wall thickening in patients with angiographically normal coronary.

纤溶酶原激活剂抑制剂导致冠状动脉造影正常的患者冠状动脉壁增厚。

• 发表时间: 2003
• 期刊: Thromb Res. 112
• 作者: Takamitsu Nakamura;et al.;Yoshihide Ichigi;Iida T;Sugiyama S;Fukushima H;Honda O:;Honda O;Miyao Y
• 通讯作者: Miyao Y

Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase - Comparison with unfractionated heparin

• DOI: 10.1016/s0735-1097(03)01059-3
• 发表时间: 2003-10-15
• 期刊: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
• 影响因子: 24
• 作者: Sakamoto, T;Ogawa, H;Okajima, K
• 通讯作者: Okajima, K