Abstract 627: Human Osteopontin Isoforms Differentially Promote Neovascularization in Response to Ischemia via Macrophage Recruitment and Survival

Background: Coronary and peripheral artery diseases result in vessel occlusion and ischemia, initiating neovascularization to restore blood flow and preserve function. We previously established that osteopontin (OPN), a matricellular cytokine, is critical to ischemia-induced neovascularization. Unlike rodents, humans express 3 OPN isoforms (a, b, and c); however, the roles of these isoforms in neovascularization and cell migration remain undefined. Methods and Results: Using a murine model of hindlimb ischemia in OPN -/- mice and 1.5x10 6 lentivirus particles expressing OPNa, OPNb or OPNc delivered IM, we found that OPN isoforms have different effects on functional perfusion recovery in vivo . OPNa increased limb perfusion 30.4%±0.8 and OPNc by 70.9%±6.3, as measured by laser Doppler perfusion imaging (d14; p2 ; 47.2%±6.1; 55.9%±6.7) and large artery (1000 - 2500 μm 2 ; 54.2%±6.1; 76.5%±10.9) ranges in vivo (n=9; p Conclusion: In conclusion, human OPN isoforms exert divergent effects on neovascularization through differential effects on arteriogenesis and macrophage migration and survival. Altogether, these data support that human OPN isoforms may represent novel therapeutic targets to improve neovascualrization and preserve tissue function in obstructive artery disease patients.