Ticagrelor (10 µM) induced an anti-apoptotic effect in hypoxic endothelial cells via increased extracellular adenosine activating A2B and A3 receptors, an effect not seen with cangrelor.
Does ticagrelor prevent endothelial cell apoptosis during hypoxia?
Ticagrelor exerts a direct, platelet-independent cytoprotective effect on hypoxic endothelial cells by increasing extracellular adenosine and activating A2B and A3 receptors.
BACKGROUND: Several studies have reported the beneficial effects of anti-platelet drugs in cardioprotection against ischaemia-reperfusion injuries. To date, no studies have focused on the indirect cytoprotective effects of ticagrelor via adenosine receptor on the endothelium. METHOD: By evaluating cell viability and cleaved caspase 3 expression, we validated a model of endothelial cell apoptosis induced by hypoxia. In hypoxic endothelial cells treated with ticagrelor, we quantified the extracellular concentration of adenosine, and then we studied the involvement of adenosine pathways in the cytoprotective effect of ticagrelor. RESULTS: Our results showed that 10 µM ticagrelor induced an anti-apoptotic effect in our model associated with an increase of extracellular adenosine concentration. Similar experiments were conducted with cangrelor but did not demonstrate an anti-apoptotic effect. We also found that A2B and A3 adenosine receptors were involved in the anti-apoptotic effect of ticagrelor in endothelial cells exposed to 2 h of hypoxia stress. CONCLUSION: we described an endothelial cytoprotective mechanism of ticagrelor against hypoxia stress, independent of blood elements. We highlighted a mechanism triggered mainly by the increased extracellular bioavailability of adenosine, which activates A2B and A3 receptors on the endothelium.
Féliu et al. (Sat,) conducted a other in Hypoxia-induced endothelial cell apoptosis. Ticagrelor vs. Cangrelor was evaluated on Endothelial cell apoptosis (cell viability and cleaved caspase 3 expression). Ticagrelor (10 µM) induced an anti-apoptotic effect in hypoxic endothelial cells via increased extracellular adenosine activating A2B and A3 receptors, an effect not seen with cangrelor.