OBJECTIVE To investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation. METHODS We performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain. RESULTS We de...

Despite the fact that lysophosphatidic acid (LPA) has been identified as a main platelet-activating lipid of mildly oxidized low-density lipoprotein (LDL) and human atherosclerotic lesions, it remains unknown whether it is capable of activating platelets in blood. We found that LPA at concentrations slightly above plasma levels induces platelet shape change, aggregation, and platelet-monocyte a...

PURPOSE Clopidogrel is a prodrug that requires transformation into an active metabolite by cytochrome P450 (CYP) in the liver in order to irreversibly inhibit the P2Y12 adenosine diphosphate platelet receptor. CYP2C19 polymorphism has been reported to correlate with reduced antiplatelet activity of clopidogrel in coronary artery disease. We assessed the association between CYP2C19 polymorphism ...

Various diagnostic and prognostic performance measures have been used to describe the clinical usefulness of platelet function testing in the evaluation and management of patients taking P2Y12 inhibitors, which reduce the risk for thrombosis due to their action on the platelet P2Y12 receptor. Platelet function tests are used to confirm the presence of an antiplatelet effect of a P2Y12 inhibitor...

OBJECTIVE The purpose of this study was to determine the effects of glucosamine and celadrin on platelet function. DESIGN Baseline values were determined on the Chronolog 570VS platelet aggregometer with whole blood aggregation impedance readings using 2 different concentrations of ADP (5 microM, 10 microM), collagen (1 microg/mL), arachidonic acid (0.5 mM/L) and an Accumetrics whole blood pl...

Inhibition of the P2Y12 pathway by the platelet antagonist clopidogrel is associated with a marked reduction in platelet reactivity. Recent reports have shown that P2Y12 inhibition has anti-inflammatory effects as well. However, whether clopidogrel withdrawal is associated with proaggregatory and proinflammatory effects has not yet been explored. Since diabetic subjects are characterized by a p...

Thromb Haemost 2006; 95: 910–1 Dear Sir, A variable response to clopidogrel is consistently observed when adenosine diphosphate (ADP)-induced platelet aggregation or vasodilator-stimulated phosphoprotein (VASP) phosphorylation is assessed in clopidogrel-treated patients (1–3). A fast, reliable and simple method to assess the degree of pharmacologic P2Y12 blockade would be of great value to asse...

OBJECTIVE Unlike currently approved adenosine diphosphate receptor antagonists, the new diadenosine tetraphosphate derivative GLS-409 targets not only P2Y12 but also the second human platelet adenosine diphosphate receptor P2Y1 and may, therefore, be a promising antiplatelet drug candidate. The current study is the first to investigate the in vivo antithrombotic effects of GLS-409. APPROACH A...

SEE PAGE 1089 T he P2Y12 receptor antagonists are key components of the medical and invasive management of coronary artery disease. These agents reduce recurrent cardiovascular events in the setting of acute coronary syndrome (ACS), decrease the incidence of thrombotic events after percutaneous coronary intervention (PCI), and prevent recurrent events in patients with histories of remote myocar...