Skip to Main content Skip to Navigation
Journal articles

Adenosine Stimulates the Migration of Human Endothelial Progenitor Cells. Role ofCXCR4 and MicroRNA-150

Abstract : BACKGROUND: Administration of endothelial progenitor cells (EPC) represents a promising option to regenerate the heart after myocardial infarction, but is limited because of low recruitment and engraftment in the myocardium. Mobilization and migration of EPC are mainly controlled by stromal cell-derived factor 1α (SDF-1α) and its receptor CXCR4. We hypothesized that adenosine, a cardioprotective molecule, may improve the recruitment of EPC to the heart. METHODS: EPC were obtained from peripheral blood mononuclear cells of healthy volunteers. Expression of chemokines and their receptors was evaluated using microarrays, quantitative PCR, and flow cytometry. A Boyden chamber assay was used to assess chemotaxis. Recruitment of EPC to the infarcted heart was evaluated in rats after permanent occlusion of the left anterior descending coronary artery. RESULTS: Microarray analysis revealed that adenosine modulates the expression of several members of the chemokine family in EPC. Among these, CXCR4 was up-regulated by adenosine, and this result was confirmed by quantitative PCR (3-fold increase, P<0.001). CXCR4 expression at the cell surface was also increased. This effect involved the A(2B) receptor. Pretreatment of EPC with adenosine amplified their migration towards recombinant SDF-1α or conditioned medium from cardiac fibroblasts. Both effects were abolished by CXCR4 blocking antibodies. Adenosine also increased CXCR4 under ischemic conditions, and decreased miR-150 expression. Binding of miR-150 to the 3' untranslated region of CXCR4 was verified by luciferase assay. Addition of pre-miR-150 blunted the effect of adenosine on CXCR4. Administration of adenosine to rats after induction of myocardial infarction stimulated EPC recruitment to the heart and enhanced angiogenesis. CONCLUSION: Adenosine increases the migration of EPC. The mechanism involves A(2B) receptor activation, decreased expression of miR-150 and increased expression of CXCR4. These results suggest that adenosine may be used to enhance the capacity of EPC to revascularize the ischemic heart.
Complete list of metadatas

Cited literature [42 references]  Display  Hide  Download

https://hal.univ-lorraine.fr/hal-01737455
Contributor : Dcac Ul <>
Submitted on : Monday, March 19, 2018 - 2:54:22 PM
Last modification on : Tuesday, October 13, 2020 - 10:46:32 AM
Long-term archiving on: : Tuesday, September 11, 2018 - 8:57:47 AM

File

journal.pone.0054135.PDF
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Magali Rolland-Turner, Emeline Goretti, Mélanie Bousquenaud, Frédérique Léonard, Christelle Nicolas, et al.. Adenosine Stimulates the Migration of Human Endothelial Progenitor Cells. Role ofCXCR4 and MicroRNA-150. PLoS ONE, Public Library of Science, 2013, 8 (1), pp.e54135. ⟨10.1371/journal.pone.0054135⟩. ⟨hal-01737455⟩

Share

Metrics

Record views

130

Files downloads

269