Adenosine A(2A) and A(3) Receptors Are Involved in the Human Endothelial Progenitor Cells Migration

作者：Fernandez Paulina; Jara Casandra; Aguilera Valeria; Caviedes Liska; Diaz Francisca; Radojkovic Claudia; Veas Carlos; Lamperti Liliana; Escudero Carlos; Aguayo Claudio^*

来源：Journal of Cardiovascular Pharmacology, 2012, 59(5): 397-404.

DOI：10.1097/FJC.0b013e3182471d14

• adenosine
• endothelial progenitor cells
• migration
• NECA

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 A(2A), A(2B), and A(3) in hEPC. Stimulation of adenosine receptors using adenosine or the nonselective agonist adenosine-5%26apos;-N-ethylcarboxamide (NECA) increased hEPC migration in 1.4-fold and 2.1-fold (P %26lt; 0.01), respectively. Stimulation of hEPC using the A(2A)-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 A(2A) 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 A(2A) and A(3) but not A(2B) receptors and provides evidence to support a role of adenosine in modulating angiogenic capacity of hEPC.

• 出版日期2012-5