LOX-1 is an adhesion molecule involved in leukocyte recruitment, the expression of VCAM-1 and ICAM-1, as well as the number of macrophages around blood vessels, were significantly increased in LOX-1 TG/ApoE KO mice compared with control mice. These reports suggest that activated LOX-1 has various aspects in cardiovascular diseases. Interestingly, previous studies have shown that LOX-1 is involved in the production of oxidant stress and inflammation after ischemia of the heart, suggesting that LOX-1 can be activated in ischemic tissues. Considering that inflammation is vital for ischemia-induced angiogenesis, LOX-1 may play an important role in SAR131675 VEGFR/PDGFR inhibitor angiogenesis after ischemia; however, little is known as to whether LOX-1 plays a role in the process of ischemia-induced angiogenesis. Accordingly, taking advantage of genetically modified LOX-1 KO mice, we examined in the present study whether LOX-1 plays a role in promoting ischemiainduced angiogenesis. LOX-1 was originally identified as the major endothelial scavenger receptor for oxidized LDL, but was subsequently detected on other cell types such as smooth muscle cells and macrophages. LOX-1 has been increasingly linked to atherosclerotic plaque formation and transgenic mouse models of gene knockout or LOX-1 overexpression also suggest that LOX-1 contributes to atherosclerotic plaque formation. On the other hand, LOX-1 ablation reduced myocardial infarct size and improved cardiac function after ischemia-reperfusion. It suggests that LOX-1 may function not only as an oxidized LDL receptor but also as a modulator of ischemic heart tissues. However, there are few reports demonstrating the role of LOX-1 as an angiogenic molecule in other ischemic tissues. Therefore, we investigated whether LOX-1 modulates angiogenesis in ischemic tissue using an ischemic hindlimb model of WT mice and LOX-1 KO mice. Interestingly, we found upregulated LOX-1 expression in the ischemic hindlimb, suggesting that ischemic status must enhance the physiological function of LOX-1. Importantly, we found that blood flow recovery in the hindlimb after ligation of femoral artery was significantly suppressed in LOX-1 KO mice compared with that in WT mice. This suggests that LOX-1 is involved in blood flow recovery in an ischemic hindlimb. Recently other groups have reported that enhanced healing/regeneration after ischemia are due to increased densities of capillaries and arterioles in the ischemic hindlimb. Therefore, we examined it and found that CD and AD in the ischemic hindlimb of LOX-1 KO mice were significantly decreased compared with that in WT mouse hindlimbs. This indicates that deletion of LOX-1 inhibits blood flow recovery via deceleration of arteriogenesis and angiogenesis after hindlimb ischemia. LOX-1 activation rapidly elevates ROS level such as superoxide anions and hydrogen peroxide via activation of a membrane-bound NADPH oxidase. Recently it has been reported that Nox2-derived ROS are involved in postischemic mobilization of bone marrow cells and revascularization. We found the suppression of Nox2 expression, ROS generation and HIF-1a expression in the ischemic hindlimb of LOX-1 KO mice in this experiment.