In the present study, both phosphorylated Akt and eNOS expression was suppressed in LOX-1 KO mice compared with that in the WT mice, as shown in Fig. 4B. Therefore, it is likely that reduced VEGF production caused less phosphorylation of Akt and eNOS and then suppressed angiogenesis and blood flow recovery. There are study limitations to be considered. As we employed conventional knockout mice and did not use the bone marrow transplantation technique to evaluate the physiological functions of LOX-1 in ischemic limbs in our study, we can not clearly demonstrate which cell, such as macrophages, endothelial cells, smooth muscle cells and so on, is the most important for the decrease in angiogenesis via LOX-1. Our results indicate that infiltrated macrophages producing VEGF and upregulated expressions of adhesion molecules such as VCAM-1 and upregulated LOX-1 itself on endothelial cells are important for angiogenesis in this experiment. Furthermore, we would like to establish a cell-specific knockout mouse model or system using bone marrow transplantation. This would give us more information to clarify the physiological functions of LOX-1. ICH often results from hypertension-induced rupture of weakened blood vessels within the brain. The exposure of brain tissue to a mass of blood components causes an inflammatory response through microglial activation and the recruitment of peripheral blood leukocytes into the perihematomal region. Blood-derived monocytes enter the ipsilateral hemisphere as early as 12 hours after ICH and constitute the largest population of peripheral leukocytes in the brain at 12 and 72 hours. There are two main subsets of monocytes in mice– the inflammatory monocytes, which express CD11b, high levels of Ly6C, and the chemokine receptor CCR2, and the patrolling monocytes that express CD11b, low levels of Ly6C, and the chemokine receptor CX3CR1. Our lab has recently shown that the Ly6Chi, CCR2+ monocytes contribute to early injury after ICH. SAR131675 CX3CR1 is a chemokine receptor found on microglia and the Ly6Clo monocyte subset. At steady state, the Ly6Clo, CX3CR1+ monocytes crawl along and patrol the endothelium. The Ly6Clo, CX3CR1+ monocytes are classically known as the “resident monocytes” and are associated with a healing phenotype. This subset of monocytes has been shown to play a pivotal role in recovery from spinal cord injury, myocardial infarction, and excitotoxic brain injury. However, conflicting reports suggest improved late recovery after spinal cord injury in chimeric mice with CX3CR1-deficient monocyte-derived macrophages. The ligand for CX3CR1, CX3CL1, is constitutively expressed by neurons and soluble CX3CL1 is increased after brain injury. In patients with acute ischemic stroke, higher plasma CX3CL1 is independently associated with better outcome. In mouse models of cerebral ischemia, exogenous CX3CL1 reduces infarct size and improves long-term outcomes, although it is unclear whether these effects are mediated by microglia or blood-derived monocytes. In a model of kainic acid-induced excitotoxic brain injury, the Ly6Clo, CX3CR1+ monocytes migrate to the injured brain and reduce neurological disability and neuronal degeneration, suggesting these monocytes have a role in neuroprotection.