Publications (2)7.49 Total impact
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Article: Dehydroepiandrosterone-sulfate inhibits thrombin-induced platelet aggregation.
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ABSTRACT: 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.Steroids 12/2011; 77(3):260-8. · 2.83 Impact Factor -
Article: Membrane lipid rafts coordinate estrogen-dependent signaling in human platelets.
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ABSTRACT: The impact of estrogens on the viability of cardiovascular system and their ability to regulate platelet function is still an open and debated question. We have previously shown that estrogen is able to significantly potentiate the aggregation induced by low doses of thrombin and to initiate a rapid and reversible signaling pathway mediated by ERbeta-directed activation of the tyrosine kinases Src and Pyk2 at the level of the plasma membrane. Lipid rafts are critical, cholesterol-enriched membrane domains, which play a major role in blood platelet activation processes. In this work, we investigated the role of lipid rafts in 17beta-estradiol signaling in human platelets. We observed that membrane rafts were essential for both 17beta-estradiol-dependent potentiation of platelet aggregation induced by subthreshold concentrations of thrombin and 17beta-estradiol-induced phosphorylation of Src. 17beta-estradiol caused the reversible translocation of ERbeta to the raft fractions and promoted the rapid and transient recruitment to, and activation within the membrane raft domains of the tyrosine kinases Src and Pyk2. The raft integrity was essential with this respect, as these effects of 17beta-estradiol were completely inhibited by cholesterol depletion. This paper provides evidence for the first time that membrane lipid rafts coordinate estrogen signaling in human platelets.Biochimica et Biophysica Acta 03/2007; 1773(2):273-8. · 4.66 Impact Factor
