Abstract 23: Exosome Inhibition Improved Blood Perfusion in Ischemic Hindlimb of db/db Diabetic Mice

Background: Critical limb ischemia (CLI), a life-threatening condition characterized by pain at rest and tissue loss with ulcer and gangrene, imposes a major public healthy burden, resulting in high mortality and disability. The occurrence of CLI in patients with diabetes mellitus is very frequent. However, the effective therapy for CLI in diabetic patients is absent. Recent studies demonstrated that exosome from diabetic animals/cells has detrimental effects on the post-injury cardiovascular repair. Here, we tested the hypotheses that exosome inhibition in vivo improves blood flow recovery and protects skeletal muscle in ischemic hindlimbs of diabetic db/db mice following surgical ischemia. Methods and Results: Exosomes were isolated from bone-marrow derived progenitor cells or plasma in non-diabetic db/+ and diabetic db/db mice by ultracentrifugation. Diabetic exosome (5 ug/ml) inhibited tube formation of human cardiac microvascular endothelial cells. Unilateral hindlimb ischemia surgery was conducted b...