Abstract 417: Changes in Endothelial Activation and Monocyte Mobilization and Recruitment in Collateral Growth Promotion/Impairment in Lean and Obese Mice

Vascular compensation to arterial occlusion is compromised by cardiovascular risk factors including obesity and hyperglycemia. The specific mechanisms mediating this impairment remain unclear. We have previously observed hindlimb collateral growth (CG), the primary compensation to peripheral artery occlusion, to be profoundly suppressed in diet-induced obese (DIO) relative to lean mice (130 vs. 10% diameter enlargement) while anti-oxidant therapy (apocynin, Apo) restored CG capacity in DIO but suppressed it in lean mice. In this study we utilize lean and DIO mice, with and without Apo treatment to assess the hypothesis that CG is impaired in obesity via redox-dependent inhibition of endothelial cell activation and reduced mobilization and/or recruitment of requisite macrophages. The right femoral artery was ligated distally to induce the gracilis artery to function as the primary collateral. The gracilis muscles of the right (exptl) and left (control) limbs were harvested 3 days post-ligation and immunostaining was performed to evaluate endothelial cell activation (# of ICAM-1 positive microvessels/mm 2 ) and macrophage recruitment (# of F4/80 positive cells/mm 2 ). ICAM-1 immunoreactivity was increased in all experimental limbs but was significant only within the DIO and Lean+Apo groups which are characterized by suppressed CG. The number of F4/80 positive cells was increased in the gracilis muscle of the experimental limb of all groups with a greater increase in the DIO than in Lean and DIO+Apo. FACS analysis of circulating monocytes demonstrated an increase at 1-day post-ligation followed by a decrease at day 3, with a greater percent decrease occurring in the DIO compared to Lean. The data suggest that mechanisms unrelated to deficits in mobilization, activation or recruitment mediate CG impairment in DIO.