Adenosine A₂A and A₃ receptors are involved in the human endothelial progenitor cells migration.
Human endothelial progenitor cells (hEPC) are recruited to sites of neovascularization where they differentiate into endothelial cells. The signals/factors responsible for hEPC migration and adhesion to sites of injury are not well understood. Elevated levels of adenosine are known to increase mature endothelial cell migration in response to tissue injury. However, the understanding of the role of adenosine in the physiology of hEPC is very limited. Using quantitative polymerase chain reaction and western blot analyses, we detected the expression of the adenosine receptors A₂A, A₂B, and A₃ in hEPC. Stimulation of adenosine receptors using adenosine or the nonselective agonist adenosine-5'-N-ethylcarboxamide (NECA) increased hEPC migration in 1.4-fold and 2.1-fold (P < 0.01), respectively. Stimulation of hEPC using the A₂A-specific agonist CGS-21680 resembled the effect observed in migration when using adenosine or NECA. Consequently, NECA and CGS-21680-stimulated migration of hEPC were reverted using the A₂A receptor antagonist ZM-241385. NECA-stimulated migration was inhibited in dose-dependent manner using MRS-1523 (Ki of 147 ± 0.016 nM), MRS-1754 (Ki of 1900 ± 0.02 nM), or ZM-241385 (Ki of 0.2 ± 0.01 nM). In conclusion, adenosine stimulates hEPC migration by activating A₂A and A₃ but not A₂B receptors and provides evidence to support a role of adenosine in modulating angiogenic capacity of hEPC.
Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
Paulina
P
Fernandez
Casandra
C
Jara
Valeria
V
Aguilera
Liska
L
Caviedes
Francisca
F
Diaz
Claudia
C
Radojkovic
Carlos
C
Veas
Liliana
L
Lamperti
Carlos
C
Escudero
Claudio
C
Aguayo
D000241:Adenosine / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D016133:Polymerase Chain Reaction; D058906:Purinergic P1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D000241:Adenosine