Background: Hydrogen sulfide (H2S), as a newly identified gaseous mediator, has been widely investigated in various systems. However, the effect of H2S 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 H2S on human platelet aggregation in vitro and its relevance to gap junction channels. Methods and results: The antiaggregatory property of H2S-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 (100μM), a conventional H2S 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 H2S is, at least in part, gap junction channel-dependent. Conclusions: H2S may inhibit human platelet aggregation at least in part by depressing gap junction intercellular communication and H2S released from ACS14 may contribute to its additional anti-platelet effect in vitro in comparison to aspirin. © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
|Titolo:||Hydrogen Sulfide Inhibits Human Platelet Aggregation In Vitro in Part by Interfering Gap Junction Channels : Effects of ACS14, a Hydrogen Sulfide-releasing Aspirin|
|Parole Chiave:||ACS14; Aspirin; Gap junction; Hydrogen sulfide; Platelet aggregation|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||gen-2015|
|Digital Object Identifier (DOI):||10.1016/j.hlc.2014.05.019|
|Appare nelle tipologie:||01 - Articolo su periodico|