Inhibitory effect of hydrogen sulfide on platelet aggregation and the underlying mechanisms

H2S (hydrogen sulfide) possesses anti-inflammatory and antioxidant capabilities and offers cardiovascular protection. The effect of H2S on platelet function, however, has been less clear. Platelet activation is a key step in the initiation and development of atherothrombotic diseases. This study explored the effects and mechanisms of H2S on human platelet in vitro and under dyslipidemia conditions. This study indicated that the collagen-induced aggregation of washed human platelets, adenosine triphosphate release, and TXA2 formation were inhibited by NaHS incubation. Furthermore, NaHS significantly decreased intracellular calcium concentration in washed human platelets stimulated with collagen and inhibited collagen-induced c-PLA2, p38 MAPK, ERK, JNK, PLC-γ2, and Akt phosphorylation. Finally, NaHS inhibited the aggregation of washed human platelets induced by oxidized low-density lipoprotein plus collagen. The level of plasma lipids and the collagen-induced rapid platelet aggregation in ApoE knockout mice were also significantly decreased by NaHS treatment. Our study shows that NaHS is able to inhibit platelet aggregation induced by collagen. The underlying mechanisms are related to NaHS-induced changes in various signaling pathways and [Ca]i in the platelets. The interaction of NaHS and platelets is also affected by lipid metabolism.