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

本研究旨在明确氧化低密度脂蛋白(OxLDL)和中性粒细胞髓过氧化物酶在急性冠脉综合征和其他代谢综合征相关疾病发病机制中的意义和可能参与的机制。这项研究主要是利用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：第一年(2004年5月至2005年3月)，我们报道了oxLDL在急性冠脉综合征罪犯病变中的定位和中性粒细胞的积聚(Am Heart J.148：818-825,2004)，以及冠状动脉粥样硬化病变中血小板激活和中性粒细胞积聚的密切关系(Int J Mol Med)。2005年15：573-537)。然后，我们分析了oxldl在人常驻巨噬细胞中的定位及其受体的表达，发现在病变中聚集的巨噬细胞中诱导了oxldl受体之一的cd36，提示…部分。巨噬细胞清道夫受体在氧化低密度脂蛋白清除中的更多释放(Long 183：109-121,2005)。在接下来的一年(2005年4月至2006年3月)，我们扩大了研究对象，以了解各种氧化因素与各种氧化应激相关疾病的发病机制是否存在一定的关系。因此，我们可以揭示oxLDL不仅在冠状动脉斑块形成和斑块不稳定中发挥重要作用，而且在支架植入后导致再狭窄的斑块炎症的延续中也发挥着重要作用(Arterioscler Thromb VASc Biol 26：877-883,2006)。氧化低密度脂蛋白还在冠状动脉病变的血栓形成和钙化中发挥作用(循环112补充2：U491,2005；循环112补充2：U585,2005)。在冠状动脉粥样硬化中，代谢综合征引起的受累器官中oxLDL的积聚并不是一种有限的现象。在脂肪性肝病中也观察到类似的结果，并与髓过氧化物酶阳性中性粒细胞的显著浸润密切相关(《肝病》43：506-514,2006)。氧化应激可能是除冠状动脉疾病以外的各种代谢综合征相关疾病发生的共同病理机制。由于血管分布在每个器官/组织中，血管的病变可能会影响整个身体。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。较少

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