A molecular pathological study of a role for oxidized low-density lipoprotein in the development of acute coronary syndrome

本研究旨在阐明氧化低密度脂蛋白（oxLDL）和中性粒细胞髓过氧化物酶在急性冠状动脉综合征（ACS）及其他代谢综合征相关疾病发病机制中的意义和潜在作用。这项研究主要是通过基于人体材料的分子病理学技术进行的。通过这个项目，我们取得了以下成果：（2004年5月-2005年3月），我们报道了急性冠状动脉综合征罪犯病变中oxLDL的定位和中性粒细胞的积聚（《美国心脏杂志》第148期：818-825,2004）以及冠状动脉粥样硬化病变中血小板活化和中性粒细胞聚集之间的密切关系15：573-537，2005）。然后，我们分析了oxLDL在人巨噬细胞中的定位及其受体表达，发现oxLDL受体之一的CD 36在病变中聚集的巨噬细胞中被诱导，这表明该部分参与了巨噬细胞的增殖。 ...更多信息 巨噬细胞清道夫受体在oxLDL清除中的作用（Lung 183：109-121，2005）。在接下来的一年中（2005年4月-2006年3月），我们扩展了研究对象，以发现各种氧化因子与各种氧化应激相关疾病的致病机制之间是否存在一定的关系。结果，我们可以发现oxLDL不仅在冠状动脉斑块形成和斑块不稳定中起重要作用，而且在导致再狭窄的支架植入后斑块炎症的持续中也起重要作用（Arterioscler Thromb Vasc Biol 26：877-883，2006）。OxLDL还在冠状动脉病变的血栓形成和钙化中发挥作用（Circulation 112 Suppl.2：U491，2005 ; and Circulation 112 Suppl.2：U 585，2005）。oxLDL在代谢综合征相关器官的蓄积并非冠状动脉粥样硬化的局限性现象。在脂肪肝疾病中观察到类似的发现，并且与髓过氧化物酶阳性中性粒细胞的显著浸润密切相关（Hepatology 43：506-514，2006）。氧化应激可能是除冠状动脉疾病之外的各种代谢综合征相关疾病的发展中的常见病理机制。由于血管分布于各个器官/组织中，血管的病变可影响全身。我想继续对氧化应激在各种代谢综合征相关疾病中的作用进行更广泛的研究。少

The present investigation aimed to clear the significance and potential participation of oxidized low-density lipoprotein (oxLDL) and neutrophil myeloperoxidase in the pathological mechanism of acute coronary syndrome and other metabolic syndrome-related diseases. The research was performed chiefly by molecular pathological techniques based on the human material. Through this project, we resulted following achievements.In the first year (May 2004 - March 2005), we reported the localization of oxLDL and the accumulation of neutrophils in culprit lesions of acute coronary syndrome (Am Heart J. 148 : 818-825, 2004) and a close association between platelet activation and neutrophil accumulation in coronary atherosclerotic lesions (Int J Mol Med. 15 : 573-537, 2005). Then, we analyzed oxLDL localization and its receptor expression in human resident macrophages, and revealed that CD36, one of the oxLDL receptors, was induced in the macrophages accumulated in the lesions, suggesting the parti … More cipation of macrophage scavenger receptor in oxLDL clearance (Lung 183 : 109-121, 2005).In the next year (April 2005 - March 2006), we extended the research objects to find if there were certain relationships between various oxidation factors and pathogenic mechanisms of diverse oxidative stress-related disorders. As a result, we could disclosed that oxLDL played an important role not only in coronary plaque formation and plaque destabilization, but also in continuation of the plaque inflammation after stenting that led to restenosis (Arterioscler Thromb Vasc Biol 26 : 877-883, 2006). OxLDL also played a role in thrombogenesis and calcification in coronary artery lesions (Circulation 112 Suppl.2 : U491, 2005 ; and Circulation 112 Suppl.2 : U585, 2005). Accumulation of oxLDL in affected organs caused from metabolic syndrome was not a limited phenomenon in coronary atherosclerosis. Similar findings were observed in fatty liver disease, and were closely related to marked infiltration of myeloperoxidase-positive neutrophils (Hepatology 43 : 506-514, 2006).Probably, oxidative stress was a common pathological mechanism in of the development of various metabolic syndrome-related diseases other than coronary artery disease. Because vessels are distributed in every organ/tissue, pathological changes in vessels may affect on a whole body. I would like to continue more extensive investigations about a role for oxidative stress in various metabolic syndrome-related diseases. Less