Molecular Pathologic Study on Roles of Oxidative Stress in Thrombogenesis in Acute Coronary Syndrome

本研究的目的是阐明氧化应激在导致急性冠脉综合征的血栓形成和进展的发病机制中的意义和作用。在本研究中，我们特别研究了髓过氧化物酶、氧化低密度脂蛋白和其他氧化相关物质之间的关系。在第一年，我们阐明了斑块内出血诱导了动脉粥样硬化切除获得的不稳定冠状动脉斑块的氧化应激(循环，114：744S，2006)，并揭示了在人类颈动脉不稳定斑块中血小板糖蛋白IIb/IIIa，P-选择素，以及中性粒细胞-血小板关联的免疫定位的新发现(心脏杂志49：406A，2007)。我们还报道了急性冠状动脉综合征患者不稳定斑块部位血栓形成与氧化应激的关系(动脉粥样硬化血栓生物，26：877-883,883)在第二年，我们扩大了研究对象，以阐明中性粒细胞髓过氧化物酶与氧化相关生物标志物的关系，包括新喋呤和S100 A8/A9复合体。我们证明了新喋呤和氧化应激在人类冠状动脉粥样硬化斑块炎症和失稳中的意义(心脏93：1537-1541,2007)。此外，我们还揭示了S100 A8/A9复合体的参与，它参与了急性冠脉综合征患者冠状动脉粥样硬化的炎症过程(心脏，2008，在新闻中)。

The aim of the present study was to clarify the significance and roles of oxidative stress in the pathogenesis of thrombus formation and progression leading to the development of acute coronary syndromes. In particular, in the present study, we investigated the relationships between myeloperoxidase, oxidized LDL, and other oxidation-related substances.In the first year, we clarified that intraplaque hemorrhage induces oxidative stress in human unstable coronary plaques obtained by atherectomy(Circulation, 114: 744S, 2006),and also revealed new findings on the immunolocalization of platelet glycoprotein IIb/IIIa, P-selectin, and neutrophil-platelet association in human carotid unstable plaques(J Am Coll Cardiol 49: 406A, 2007).We also reported the relationship between thrombosis at the site of unstable plaques and oxidative stress in patients with acute coronary syndromes(Atherosler Thromb Vas Biol, 26: 877-883, 2006).In the second year, we extended the research objects to clarify the relationship between neutrophil myeloperoxidase and oxidation-related biomarkers including neopterin and S100 A8/A9 complex. We demonstrated the significance of neopterin and oxidative stress in plaque inflammation and destabilization of human coronary atherosclerotic lesions(Heart 93: 1537-1541, 2007).We moreover revealed the participation of S100 A8/A9 complex, which was involved in the inflammatory process of coronary atherosclerosis in patients with acute coronary syndromes(Heart, 2008, in press).