Abstract WP100: Hydrogen Sulfide Increases Angiogenesis And Improves Functional Outcome After Stroke
Background: Hydrogen Sulfide is a potent inducer of angiogenesis. In this study, we investigate whether NaHS (H2S donor) induces angiogenesis and thereby improves functional outcome in rat cerebral ischemic/reperfusion model.
Methods: Adult male rats were subjected to middle cerebral artery occlusion and were treated with 5mg/kg of NaHS or normal saline starting 48 hours after middle cerebral artery occlusion and daily for 14 days. Neurological functional tests were performed. The volume of von willebrand factor(vWF)- positive area was measured. Newly proliferated vascular endothelial cell were counted. Angiogenic factor expressions were measured by immunohistochemistry and western blot. In vitro, endothelial tube formation was examined.
Result: NaHS significantly promoted vWF-positive area (30.1±10.1% vs. vehicle, 12.3±7.1 %, p<0.01) and proliferation of vascular endothelial cell (7.3/2*105 um2 vs. vehicle, 3.1/2*105um2, p<0.01) in the ischemic brain. and improved functional outcome after stroke. Mechanisms underlying the NaHS-induced vascular remodeling were investigated. NaHS increased the expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1), angiopoietin-2(Ang-2) and phosphorylation of Akt, and ERK-1/2.
Conclusions: NaHS promoted angiogenesis, which may contribute to improvement of functional outcome after stroke. The VEGF/VEGF receptor, phosphoinositide 3-kinase/Akt, and ERK-1/2 pathways appear to mediate NaHS-induced angiogenesis.
- © 2012 by American Heart Association, Inc.