Abstract 13439: Arteriogenesis is Impaired in CSEKO Mouse Hind Limb Ischemia Due to Attenuated Expression of Chemokines and Cytokines
Introduction Collateral growth due to arteriogenesis is a major mechanism to restore blood flow during chronic tissue ischemia. Arteriogenesis involves outward vascular remodeling of collateral arteriole to reestablish bulk blood flow to ischemic tissue that is mediated by mechanical forces and cytokine/chemokine expression. Cystathionine gama lyase (CSE), is a dominant enzyme producing hydrogen sulfide (H2S) in vascular tissues that we have previously shown modulates ischemic angiogenesis. However, regulation of arteriogenesis responses by H2S during hind limb ischemia remains unknown.
Hypothesis To determine the effect and molecular mechanisms of H2S on arteriogenesis during hind limb ischemia in the CSE knockout (KO) mouse.
Method Left femoral artery ligation and excision were performed in wild type (WT) and CSEKO mice (n=8, each group). Hind limb perfusion was measured using a laser Doppler perfusion probe. Arteriogenesis was determined by NOVADEQ SPY imaging and fluorescence staining of hind limb skeletal muscle by anti CD31, anti- α-SMA and DAPI staining. Monocyte recruitment was determined by positive staining with anti mouse MAC-2 and DAPI. Interleukin (IL) -16, IL-19, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) level were measured by ELISA.
Result Blood flow recovery was significantly impaired in CSEKO mice compared to WT mice. Blush rate by SPY imaging and SMA positive mature vessel density were impaired in CSEKO mice. Although there was no difference in recruitment of monocytes in non-ischemic tissue, monocyte recruitment was significantly impaired in ischemic tissue of CSEKO mice compared to WT mice. Expression of IL-16, IL-19, VEGF and bFGF were also significantly attenuated in ischemic tissue of CSEKO mice compared to WT mice. Conclusion Restoration of blood flow was impaired in CSEKO mice due to impaired arteriogenesis. Impairment of arteriogenesis was associated with decreased immune cell recruitment and expression of chemokines and cytokines during ischemia in CSEKO mice.
- © 2012 by American Heart Association, Inc.