SDF-1 is an Important Cytokine for Neovascularization. Cleavage of SDF-1 is Reduced by DPPIV Inhibitors
Conditions
Keywords
CAD, diabetes, SDF-1, endothelial function
Brief summary
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.
Detailed description
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.
Interventions
DRUGVildagliptin
Vildagliptin, 50 mg twice a days, orally for 30 days followed by placebo
Sponsors
Johann Wolfgang Goethe University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with diabetes mellitus type 2 under stable medication * HbA1c between 7% an 10% * age between 18 and 80 years * signed informed consent
Exclusion criteria
* Atrial fibrillation (plethysmographic recordings can only obtained in sinus-rhythm) * CAD with reduced left ventricular ejection fraction (LVEF \<45%) * Pregnancy, chronic or acute infection, fever * Diabetes mellitus type 1 * Newly diagnosed diabetes, uncontrolled diabetes * Neoplasm * Known allergy to study drug * Severe liver/kidney disease * HIV, Hepatitis * Participation at other studies within the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endothelial Function | 30 days |
Secondary
| Measure | Time frame |
|---|---|
| Number and Function of Progenitor Cells | 30 days |
Countries
Germany
Outcome results
None listed