Abstract: Abstract: Objective: Thromboxane A2 (TxA2) that derived from platelets can facilitate atherosclerosis and thrombosis, participating in the occurrence, development and progression of cardiovascular diseases. It has been indicated that dietary intervention plays vital roles in early prevention and treatment of cardiovascular diseases. Coenzyme Q10 (CoQ10) has promising cardiovascular benefits due to extensive biological activities, including anti-oxidation, anti-inflammation and improving disorders of glucose and lipid metabolism. We previously demonstrated that CoQ10 attenuated platelet activation, aggregation and thrombus formation. However, the role of CoQ10 in platelet TxA2 generation has never been explored. Our present study aims to investigate whether CoQ10 acts on TxA2 generation as well as to clarify the underlying mechanisms. Methods: Gel-filtered platelets prepared from heathy adults were incubated with different concentrations of CoQ10 (0, 1, 10, or 100 μmol/L) for 50 min. After agonist activation, the levels of TxB2 that secreted from platelets were determined by enzyme-linked immunosorbent assays (because TxA2 is unstable after generation, the levels of its stable metabolite, TxB2, are used to reflect TxA2 generation). The phosphorylation of cytosolic phospholipase A2 (cPLA2) was measured by Western blot. Results: CoQ10 significantly inhibited platelet TxA2 generation that induced by several agonists, including thrombin, collagen and convulxin. The results from Western blot showed that CoQ10 significantly down-regulated thrombin- and collagen-induced cPLA2 phosphorylation. Moreover, pyrrophenone, one cPLA2 specific inhibitor, showed no any additive effects on TxA2 generation when combined with CoQ10. Furthermore, agonist-induced platelet cPLA2 phosphorylation and TxA2 generation were almost completely reversed by protein kinase A (PKA) inhibitor H89. Conclusions: CoQ10 can attenuate agonist-induced platelet TxA2 generation, and the mechanism is mainly through regulating PKA/cPLA2 signaling pathway.

Key words: Coenzyme Q10, platelet, thromboxane A2, cytosolic phospholipase A2, cardiovascular diseases