Hydrogen Sulfide Inhibits Human Platelet Aggregation In Vitro in Part by Interfering Gap Junction Channels: Effects of ACS14, a Hydrogen Sulfide-releasing Aspirin.

Background Hydrogen sulfide (H 2 S), as a newly identified gaseous mediator, has been widely investigated in various systems. However, the effect of H 2 S on cardiovascular system haemostasis, including platelet aggregation and the precise mechanisms remain unclear. Therefore, the present study was aimed to examine the inhibitory effect of H 2 S on human platelet aggregation in vitro and its relevance to gap junction channels. Methods and results The antiaggregatory property of H 2 S-releasing aspirin derivative (ACS14) was compared with its mother compound, aspirin. In comparison to an equimolar dose of aspirin, ACS14 not only exerted a more potent inhibitory effect on platelet aggregation induced by ADP or thrombin, but also significantly inhibited αIIbβ3 integrin activation and P-selectin expression. Similarly, NaHS (100 μM), a conventional H 2 S donor significantly inhibited platelet aggregation as well as αIIbβ3 integrin activation and P-selectin expression induced by ADP or thrombin. Furthermore, pretreatment with rotigaptide, a gap junction modifier abolished the inhibitory properties of ACS14 or NaHS on platelet aggregation, suggesting that suppression of platelet aggregation by H 2 S is, at least in part, gap junction channel-dependent. Conclusions H 2 S may inhibit human platelet aggregation at least in part by depressing gap junction intercellular communication and H 2 S released from ACS14 may contribute to its additional anti-platelet effect in vitro in comparison to aspirin. [ABSTRACT FROM AUTHOR]