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

我们研究了急性冠脉综合征(ACS)患者的凝血和纤溶活性。纤溶酶原激活物抑制物(PAI-1)是纤溶系统的主要控制因子。PAI-1与冠状动脉内血栓的出现和消失密切相关，并与冠状动脉疾病的预后密切相关。已有研究表明，急性冠脉综合征患者PAI-1水平升高。PAI-1升高与内脏脂肪含量显著相关。换句话说，肥胖患者的PAI-1水平升高。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，肥胖者血浆非酯化脂肪酸(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影响脂肪组织产生PAI-1，我们研究了培养的小鼠脂肪组织(3T3-L1脂肪细胞)产生PAI-1的情况。在所有主要的NEFA中，…在血浆中，含有油酸和亚麻酸等不饱和池塘的NEFA更能刺激细胞产生PAI-1。与饱和NEFA相比，PAI-1活性与冠状动脉疾病的预后密切相关，维持较低水平尤为重要。本文阐述了静脉注射活化蛋白C(APC)作为急性心肌梗死溶栓治疗的联合治疗，对预防溶栓治疗再通的梗塞相关冠状动脉的再闭塞是有效的。APC不仅抑制Va和VIIIa因子，而且还抑制PAI-1。在慢性缺血性心脏病患者中，口服尼可地尔也能有效地降低PAI-1的活性。其他降低血浆PAI-1水平的药物干预包括抑制NEFA对脂肪细胞产生PAI-1。贝特类药物可以降低甘油三酯水平，并诱导NEFAs的β氧化。还需要进一步的实验和临床检查。较少

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