کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2028239 | 1070403 | 2012 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Dehydroepiandrosterone-sulfate inhibits thrombin-induced platelet aggregation Dehydroepiandrosterone-sulfate inhibits thrombin-induced platelet aggregation](/preview/png/2028239.png)
Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are the most abundant steroids circulating in human blood. DHEA stimulates endothelial cells to release high amounts of nitric oxide in the circulation. Nitric oxide activates guanylyl cyclase in platelets thus decreasing the responsiveness of these cells to physiological agonists. However, the impact of DHEA-S and DHEA on platelet function and their possible role in modulating the response of human platelets to physiological agonists were not yet investigated. Here, DHEA-S, but not DHEA, inhibited in vitro thrombin-dependent platelet aggregation in a dose-dependent manner. DHEA-S exerted this effect by decreasing thrombin-dependent dense granule secretion, and so impairing the positive feed-back loop provided by ADP. Furthermore, DHEA-S inhibited thrombin-dependent activation of Akt, ERK1/2, and p38 MAP kinase. Although both DHEA-S and DHEA directly activated in platelets the inhibitory cGMP/PGK/VASP pathway, these events were not responsible for the inhibitory action of DHEA-S in platelets. In addition DHEA-S acted in synergism with nitric oxide in inhibiting platelet aggregation. In conclusion DHEA-S inhibited platelet activation caused by a mild stimulus without completely hampering platelet functionality and thus DHEA-S may participate in the physiological mechanisms that maintain circulating platelets in a resting state. The role played by DHEA-S could be relevant mainly when the functionality of the vascular endothelium is compromised.
► DHEA-S inhibits platelet aggregation induced by thrombin, collagen, and thromboxane A2.
► DHEA-S inhibits dense granule release and phosphorylation of Akt, ERK1/2, and p38 MAPK.
► Exogenous ADP reverts DHEA-S inhibition of platelet aggregation and phosphorylation.
► DHEA-S and DHEA directly activate the inhibitory cGMP/PGK/VASP pathway in platelets.
► The activation of the NO/cGMP/PGK pathway is not involved in DHEA-S inhibitory action.
Journal: Steroids - Volume 77, Issue 3, February 2012, Pages 260–268