Abstract 14187: Passive Exercise Using Whole Body Periodic Acceleration Device Promotes Angiogenesis in a Mice Model of Hindlimb Ischemia
Introduction: The whole body periodic acceleration (WBPA) system has been developed as a “passive exercise” device to improve endothelial function by increasing endothelial shear stress through repetitive movement in the direction of the spinal axis. To date, the impact of WBPA on ischemia-induced angiogenesis has not been investigated.
Hypothesis: Passive exercise promotes angiogenesis in a mouse model of hindlimb ischemia.
Methods: After left femoral artery excision, wild-type (WT) mice were assigned one of two groups: The WBPA group (n=18) received WBPA at 150 cycles/min for 45min every day. The control group (n=20) were anesthetized but remained sedated. Hindlimb blood flow was assessed by laser doppler perfusion imaging (LDPI) and capillary density was assessed by CD31 staining. Endothelial nitric oxide synthase (eNOS) activation in aorta and skeletal muscle was analyzed by western blot analysis. Comprehensive protein array analysis was performed to identify skeletal muscle-derived angiogenic growth factors.
Results: In WT mice, WBPA-treated mice showed a significant increase in flow recovery at 7 days after ischemic surgery as determined by LDPI analysis (p=0.02). Quantitative histological analysis revealed that the capillary density was significantly increased in WBPA-treated mice compared with control mice on postoperative day 14, suggesting that revascularization was occurred at the microcirculatory level. These changes were associated with an increase in eNOS phosphorylation in aorta and skeletal muscle. The pro-angiogenic effect of WBPA on ischemic limb was blunted in eNOS deficient mice indicating that the stimulatory action of WBPA on revascularization is dependent on eNOS. In addition, comprehensive protein array analysis revealed that the panel of angiogenic growth factors was upregulated in skeletal muscle by WBPA suggesting that muscle-derived angiogenic factors might contribute to collateral formation in WT mice.
Conclusions: WBPA stimulates revascularization in response to ischemic insult through its ability to activate eNOS signaling axis and upregulate the expression of angiogenic growth factor in skeletal muscle. WBPA may serve as a powerful non-invasive intervention to facilitate therapeutic angiogenesis.
- © 2010 by American Heart Association, Inc.