Abstract 21415: Exercise-induced Changes In Angiogenesis, Arteriogenesis and Vascular Integrity are eNOS-NO Dependent in Mice With Hindlimb Ischemia
Introduction: Exercise training is assumed to improve skeletal muscle function in the presence of peripheral arterial disease (PAD); however, the mechanisms are unclear. Nitric oxide (NO) plays an important role on the cardiovascular system in response to ischemic injury; however, controversy remains regarding the role of endothelial NO synthase (eNOS)-derived NO on angiogenesis, arteriogenesis, and vascular integrity after exercise.
Methods: Female wild-type (WT) mice (n=45) and eNOS-/- mice (n=45) were assigned to one of 3 groups: 1) control sedentary (SED); 2) hindlimb ischemia (HLI); 3) HLI with swimming (HLI-SW), which constituted 60 min swimming twice a day, 5 days/week for 14 days. Subsets of animals (n=6) were injected with 99mTc-labeled RGD-peptide (GE-078) targeted at activated av integrins to assess angiogenesis. Angiogenesis was assessed by α-well counting of radioactive activity, and an ischemic (I) to non-ischemic (NI) ratio calculated. Arteriogenesis was evaluated by microCT angiography (mCTA) following ex vivo vascular casting (n=6). Subgroups had immunohistochemical staining for capillary density (n = 3). In addition, vascular integrity was assessed with in vivo contrast mCTA in 6 WT and 6 eNOS-/- mice after HLI with or without SW. All analyses were performed 14 days post-HLI.
Results: The GE-078 uptake was increased with HLI compared to SED mice both in WT and eNOS-/- mice, however, SW increased uptake of GE-078 only in eNOS-/--HLI-SW mice (Figure). This later increase was associated with decreased capillary density and increased arteriogenesis (<48 μm). In vivo contrast mCTA demonstrated late contrast retention in eNOS-/-HLI mice suggesting disruption of vascular integrity, which worsened with SW.
Conclusions: Integrin activation was greater in eNOS-/--HLI mice and was augmented with exercise, however was associated with disruption of vascular integrity. NO does appear to play a role in the effects of exercise training in a model of PAD.
- © 2010 by American Heart Association, Inc.