Figure 6: Schematic Model of Platelet ABCC4 Role in HIV

In HIV, circulating platelets have increased expression of ABCC4 as consequence of enhanced platelet activation. ABCC4 overexpression on platelet plasma membrane contributes to increased excretion of platelet mediators in the extracellular space, including cAMP, which plays a crucial role in maintaining platelets in the inactive state. In turn, platelet inflammatory mediators activate endothelial cells and monocytic cells, and also platelets, promoting the formation of circulating platelet aggregates. The large amount of S1P released by activated platelets likely contributes to amplify platelet response and the inflammatory process in HIV. Platelet ABCC4 inhibition by Ceefourin in HIV prevents platelet activation by maintaining cAMP homeostasis. Moreover, the inhibition of ABCC4 has an important role in mediating platelet–cell interaction and the inflammatory response in HIV, by decreasing platelet-mediator release and activation of target cells in circulation. Abbreviations as in Figure 1.



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