SDF-1 is an Important Cytokine for Neovascularization. Cleavage of SDF-1 is Reduced by DPPIV Inhibitors Clinical Trial
Official title:
Functional Improvement of Progenitor Cells and Endothelial Function by Vildagliptin in Diabetes Mellitus (FINNjA-DM).
SDF-1, an important cytokine for neovascularisation is cleaved by (dipeptidyl peptidase IV)
DPPIV.
The aim of this study is to assess the effect of the dipeptidyl peptidase IV inhibitor
vildagliptin (Galvus®) on endothelial function as well as number and functional activity of
progenitor cells in patients with documented diabetes mellitus.
The peptidase CD26 (DPPIV/dipeptidyl peptidase IV) removes dipeptides from the amino terminus
of proteins and thereby inactivates these cleaved proteins. It was shown, that CD26 cleaves
SDF-1 into a non-mitogenic molecule. Inhibition or deletion of CD26 leads to an increased
homing of hematopoietic progenitor cells to the bone marrow after transplantation by
increasing the invasion capacity of these cells {Campbell et al. 2008; Christopherson et al.
2004}.
The cytokine SDF-1 is released in response to hypoxia, is crucial for progenitor cell homing
and recruitment of cells for neovascularisation. Invasion capacity is closely related to the
cytokine SDF-1 and the SDF-1 receptor CXCR4 {Ceradini et al. 2004}. The in vivo
neovascularisation capacity of progenitor cells is closely correlated to their functional
capacity as SDF-1 induced invasion or colony-forming capacity {Heeschen et al. 2004; Britten
et al. 2003; Assmus et al. 2007}.
Therefore, the aim of this study is to assess the effect of the dipeptidyl peptidase IV
inhibitor vildagliptin on endothelial function as well as number and functional activity of
progenitor cells in patients with documented diabetes mellitus.
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