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

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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.