Abstract 18967: Inhibition of Circulating Exosome Improved Ischemic Hindlimb Repair in Type Diabetic db/db Mice

Background: Recent studies have demonstrated that exosomes from diabetic animals/cells have detrimental effects on the post-injury vascular repair. Here, we tested the hypothesis that systemic exosome inhibition in vivo improves blood flow recovery in ischemic hindlimbs of diabetic db/db following surgical ischemia. Methods and Results: Exosomes were isolated from plasma of non-diabetic db/+ and diabetic db/db mice by standard ultracentrifugation method. Unilateral hindlimb ischemia surgery was conducted by ligation of left femoral artery in 12-week old, male db/+ and db/db mice. Exosome inhibitor GW-4869 (GW, 2 μg/g body weight) was administrated by intraperitoneal injection every other day for 4 weeks starting from one week before the hindlimb ischemia (HLI) surgery. HLI mice injected with vehicle served as controls. Mice were divided into four groups: 1) db/+ + vehicle; 2) db/db+ vehicle; 3) db/+ GW; 4) db/db + GW. We found that systemic administration of GW decreased necrosis and loss of toe/toenail, ...