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Cyclophilin A modulates bone marrow-derived CD117+ cells and enhances ischemia-induced angiogenesis via the SDF-1/CXCR4 axis
- Source :
- International Journal of Cardiology. 212:324-335
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Background Critical limb ischemia (CLI) is a major health problem with no adequate treatment. Since CLI is characterized by insufficient tissue vascularization, efforts have focused on the discovery of novel angiogenic factors. Cyclophilin A (CyPA) is an immunophilin that has been shown to promote angiogenesis in vitro and to enhance bone marrow (BM) cell mobilization in vivo . However, its potential as an angiogenic factor in CLI is still unknown. Thus, this study aimed to evaluate whether CyPA might induce neo-angiogenesis in ischemic tissues. Methods and results Wild-type C57Bl/6j mice underwent acute hind-limb ischemia (HLI) and received a single intramuscular administration of recombinant CyPA or saline. Limb perfusion, capillary density and arteriole number in adductor muscles were significantly increased after CyPA treatment. Interestingly, BM-derived CD117 + cell recruitment was significantly higher in ischemic adductor tissue of mice treated with CyPA versus saline. Therefore, the effect of CyPA on isolated BM-derived CD117 + cells in vitro was evaluated. Low concentrations of CyPA stimulated CD117 + cell proliferation while high concentrations promoted cell death. Moreover, CyPA enhanced CD117 + cell adhesion and migration in a dose-dependent manner. Mechanistic studies revealed that CyPA up-regulated CXCR4 in CD117 + cells and in adductor muscles after ischemia. Additionally, SDF-1/CXCR4 axis inhibition by the CXCR4 antagonist AMD3100 decreased CyPA-mediated CD117 + cell recruitment in the ischemic limb. Conclusion CyPA induces neo-angiogenesis by recruiting BM-derived CD117 + cell into ischemic tissues, at least in part, through SDF-1/CXCR4 axis.
- Subjects :
- 0301 basic medicine
Programmed cell death
Pathology
medicine.medical_specialty
Receptors, CXCR4
Angiogenesis
Cell
Ischemia
Neovascularization, Physiologic
Cypa
Bone Marrow Cells
030204 cardiovascular system & hematology
CD117+ cells
03 medical and health sciences
Mice
0302 clinical medicine
Cell Movement
medicine
Cell Adhesion
Animals
Humans
Cell adhesion
Cells, Cultured
Cell Proliferation
biology
Cell growth
business.industry
medicine.disease
biology.organism_classification
Hind-limb ischemia
digestive system diseases
Chemokine CXCL12
3. Good health
Hindlimb
Mice, Inbred C57BL
Disease Models, Animal
Proto-Oncogene Proteins c-kit
030104 developmental biology
medicine.anatomical_structure
Cancer research
Bone marrow
business
Cardiology and Cardiovascular Medicine
SDF-1/CXCR4 axis
Cyclophilin A
Neo-angiogenesis
Signal Transduction
Subjects
Details
- ISSN :
- 01675273
- Volume :
- 212
- Database :
- OpenAIRE
- Journal :
- International Journal of Cardiology
- Accession number :
- edsair.doi.dedup.....2c9256181b040e9d92be501cb88ae819
- Full Text :
- https://doi.org/10.1016/j.ijcard.2016.03.082