Wang MJ, Cai WJ, Li N, Ding YJ, Chen Y, Zhu YC
The Hydrogen Sulfide Donor NaHS Promotes Angiogenesis in a Rat Model of Hind Limb Ischemia. [JOURNAL ARTICLE]
Antioxid Redox Signal 2009 Oct 20.
It is not known whether H2S can promote angiogenesis with improvement of regional blood flow in ischemic organs. Sodium hydrosulfide (NaHS, a H2S donor) was administered once a day for 4 w following femoral artery ligation. Collateral vessel growth, capillary density, regional tissue blood flow, the expression of endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and Akt were examined during or at the end of the treatment period. NaHS treatment significantly increased collateral vessel growth, capillary density and regional tissue blood flow in ischemic hindlimb muscles compared with the controls. These effects were associated with an increase in VEGF expression in the skeletal muscles and VEGFR2 phosphorylation in the neighboring vascular endothelial cells suggesting a role of VEGF in mediating the NaHS effects in a cell-cell interaction pattern. Moreover, NaHS treatment also resulted in an increase in Akt phosphorylation in ischemic hindlimb muscles. In conclusion, our observations with NaHS strongly suggest that H2S is a proangiogenic factor in chronic ischemia. The pro-angiogenic effect of NaHS may be mediated by interaction between the up-regulated VEGF in the skeletal muscle cells and the VEGFR2 as well as its downstream signaling element Akt in the vascular endothelial cells.
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