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Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system
- Source :
- American journal of physiology. Regulatory, integrative and comparative physiology. 294(3)
- Publication Year :
- 2007
-
Abstract
- Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.
- Subjects :
- Male
Physiology
medicine.medical_treatment
Dipeptidyl Peptidase 4
Myocytes, Smooth Muscle
Neovascularization, Physiologic
Pharmacology
Endothelial progenitor cell
Mice
Ischemia
Physiology (medical)
Precursor cell
Cyclosporin a
medicine
Animals
Humans
Progenitor cell
Cells, Cultured
Bone Marrow Transplantation
Microscopy, Confocal
business.industry
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells
Endothelial Cells
Flow Cytometry
Matrix Metalloproteinases
Hindlimb
Transplantation
Endothelial stem cell
Mice, Inbred C57BL
Cytokine
medicine.anatomical_structure
Immunology
cardiovascular system
Cyclosporine
Cytokines
Bone marrow
business
Immunosuppressive Agents
Subjects
Details
- ISSN :
- 03636119
- Volume :
- 294
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Accession number :
- edsair.doi.dedup.....0baae40274cd3c511546c95a7cfd949d