SDF-1α dependent effects of aliskiren on neovasculogenesis after hindlimb ischemia.

<p>In color-coded images, red indicates normal perfusion and blue indicates a marked reduction in blood flow in the ischemic hindlimb. Quantitative analysis of the LDI ratio for foot blood flow in animals before, immediately after, and 2 weeks after the surgery of hindlimb ischemia. Compared with aliskiren (25 mg/kg/day) treatment alone, aliskiren (25 mg/kg/day) in combination of anti-SDF-1 mAb treatment significantly impaired blood flow recovery after hindlimb ischemia (n = 6 in each group; A, B). Anti-CD31 immunostaining showed decreased number of capillary formation in the animals with both aliskiren and anti-SDF-1 mAb treatment as compared with that with aliskiren treatment alone (n = 6; C). Ischemia-induced EPC-like cell mobilization was determined by flow cytometry. Compared with aliskiren treatment alone, the combination of aliskiren and anti-SDF-1 mAb treatment significantly attenuated the number of circulating EPCs (n = 6; D). ELISA data showed that the amount of SDF-1 in plasma of aliskiren high dose (25 mg/kg/day) with anti-SDF-1 neutralizing antibody was significantly lower than control (untreated DM mice; vehicle (PBS)-treated mice) (n = 6; E). SDF-1 protein was abolished in index thigh muscles by the neutralizing antibody after injection of anti-SDF-1 neutralizing antibody for 2 weeks (n = 6; F). Statistical analysis was done by unpaired Student’s t test or analysis of variance, followed by Scheffe’s multiple-comparison <i>post hoc</i> test. A p value of <0.05 was considered statistically significant. *<i>p</i> < 0.05, **<i>p</i> < 0.01.