The hydrogen sulfide donor NaHS promotes angiogenesis in a rat model of hind limb ischemia.
It is not known whether H(2)S can promote angiogenesis with improvement of regional blood flow in ischemic organs. Sodium hydrosulfide (NaHS, a H(2)S 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 hind limb 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 hind limb muscles. In conclusion, our observations with NaHS strongly suggest that H(2)S is a proangiogenic factor in chronic ischemia. The proangiogenic effect of NaHS may be mediated by interaction between the upregulated VEGF in the skeletal muscle cells and the VEGFR2 as well as its downstream signaling element Akt in the vascular endothelial cells.
Wang
Ming-Jie
MJ
Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, China.
Cai
Wen-Jie
WJ
Li
Na
N
Ding
Ying-Jiong
YJ
Chen
Ying
Y
Zhu
Yi-Chun
YC
D000818:Animals; D002450:Cell Communication; D042783:Endothelial Cells / Q000166:cytology; D005121:Extremities / Q000473:pathology*; D006439:Hemodynamics; D006862:Hydrogen Sulfide / Q000737:chemistry*; D007511:Ischemia; D008297:Male; D009389:Neovascularization, Pathologic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; C025451:sodium bisulfide; D006862:Hydrogen Sulfide