Clarification of the mechanisms of cardiovascular dysfunction and the resultant organ failure

越来越多的证据表明氧化LDL受体LOX-1在内皮和血管功能障碍中的重要性。在这项研究中，我们产生了LOX-1 KO小鼠来研究LOX-1在动脉粥样硬化疾病中的作用。对于KO小鼠，我们获得了以下结果。(1)LOX-1 KO小鼠对氧化LDL对内皮依赖性舒张的抑制作用具有抗性。(2)在C57 BL/6和LDLRKO-C57 BL/6背景下，与野生型小鼠相比，LOX-1 KO小鼠中高脂饮食诱导的动脉粥样硬化延迟。(3)与野生型相比，LOX-1基因敲除小鼠的LASD结扎诱导的心肌梗死和心脏重构受到抑制，心脏功能相对保留。(4)与野生型相比，LOX-1 KO小鼠的体外血小板聚集和体内FeCl 2诱导的血栓形成均受到抑制。因此，我们已经证明LOX-1参与动脉粥样硬化疾病的每个阶段，即内皮功能障碍、动脉粥样硬化、血栓形成和心肌梗死。

Accumulating evidence suggests significance of the oxidized LDL receptor LOX-1 in endothelial and vascular dysfunction. In this study, we generated LOX-1 KO mice to address the role of LOX-1 in atherosclerotic diseases. With the KO mice, we obtained following results. (1) LOX-1 KO mice were resistant to the suppressive effects of oxidized LDL on endothelium-dependent relaxation. (2) Atherosclerosis induced by high fat diet was delayed in LOX-1 KO mice compared with wild type mice in both C57BL/6 and LDLRKO-C57BL/6 background. (3) Myocardial infarction and cardiac remodeling induced by LASD ligation was suppressed and cardiac function was relatively preserved in LOX-1 KO mice compared with wild type. (4) Both platelet aggregation in vitro and FeC12-induced thrombosis in vivo were suppressed in LOX-1 KO mice compared with wild type. Thus, we have demonstrated that LOX-1 aggravates every phase of atherosclerotic diseases, i.e. endothelial dysfunction, atherosclerosis, thrombosis, and myocardial infarction.