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

点击翻译按钮获取中文摘要

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