Why the study?
ADP receptors and PKC isoforms play different roles in platelet activity, but their interaction in whole blood platelet adhesion under flow conditions was unclear.
P2Y12 and PKCδ signaling synergistically stimulate platelet adhesion under high shear flow conditions, highlighting a potential mechanistic target for inhibiting the initial steps of thrombus formation.
These in vitro findings on platelet adhesion are hypothesis-generating; clinical relevance of P2Y and PKC modulation remains to be determined.
Adenosine diphosphate (ADP) receptors and protein-kinase C (PKC) isoforms play different role in platelet activity. In the present study, whole blood platelet adhesion at 200 - 1800 s-1 shear rates was investigated by Impact-R system, measuring percent of surface coverage (SC) by platelets. Gradual heightened shear rate par-alleled increase of platelet adhesion. At relatively low shear (200 and 1000 s-1) blockade of neither P2Y1 receptor nor P2Y12 receptor (by A2P5P and 2MeSAMP, respectively) affected SC. At high shear rate (1800 s-1) reduction of SC was observed by 2MeSAMP. Treatment of blood with PKCδ inhibitor (rottlerin) but not PKCα,β inhibitor (Gö6976) diminished platelet adhe-sion. Among all the agents, only combination of 2MeSAMP and rottlerin used at subthreshold concentrations was able to inhibit platelet adhesion under high shear condition. We suggest that platelet agonist-induced P2Y12 and PKCδ signaling essentially stimulates platelet adhesion under flow condition, the important initiating step of thrombin formation.
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Shenkman et al. (2023) studied this question.
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