OBJECTIVES The purpose of this study was to assess the in vitro P2Y12 receptor inhibitory effects of cangrelor on platelets from patients on maintenance prasugrel therapy treated with 2 reloading dose regimens. BACKGROUND Despite its more potent and rapid antiplatelet effects compared with clopidogrel, recent studies have shown variability in prasugrel-mediated P2Y12 receptor inhibition, part...

BACKGROUND Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel. OBJECTIVES To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitorin...

The aim was to investigate the beneficial effects of clopidogrel in thoracic aorta function and structure and to characterize if P2Y12 receptors contribute to these effects. Male Sprague Dawley rats were infused with angiotensin II [(Ang II) 60 ng x min(-1), 14 days] or saline (control rats) and were simultaneously treated with clopidogrel (10 mg x kg(-1) x day(-1)) or vehicle. After 14 days, s...

BACKGROUND Diadenosine tetraphosphate (Ap4A), a constituent of platelet dense granules, and its P1,P4-dithio and/or P2,P3-chloromethylene analogs, inhibit adenosine diphosphate (ADP)-induced platelet aggregation. We recently reported that these compounds antagonize both platelet ADP receptors, P2Y1 and P2Y12. The most active of those analogs, diadenosine 5',5″″-P1,P4-dithio-P2,P3-chloromethylen...

Dual antiplatelet treatment (DAPT) with aspirin and a P2Y12 receptor antagonist is essential for patients presenting with acute coronary syndrome (ACS) irrespective of their specific percutaneous coronary intervention (PCI). Clopidogrel (Bristol-Myers Squibb/Sanofi Pharmaceuticals, Bridgewater, NJ, USA), one of the most popular P2Y12 receptor antagonists of the past decade, has reduced the risk...

The small GTPase RAP1 is critical for platelet activation and thrombus formation. RAP1 activity in platelets is controlled by the GEF CalDAG-GEFI and an unknown regulator that operates downstream of the adenosine diphosphate (ADP) receptor, P2Y12, a target of antithrombotic therapy. Here, we provide evidence that the GAP, RASA3, inhibits platelet activation and provides a link between P2Y12 and...

Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activit...

Adenosine 5 -diphosphate (ADP) plays a central role in regulating platelet function by the activation of the G protein–coupled receptors P2Y1 and P2Y12. Although it is well established that aggregation responses of platelets to ADP desensitize, the underlying mechanisms involved remain unclear. In this study we demonstrate that P2Y1and P2Y12-mediated platelet responses desensitize rapidly. Furt...

BACKGROUND AND PURPOSE: A recent study identified a preprocedural P2Y12 reaction units value of 60 or 240 as a strong independent predictor of perioperative thromboembolic and hemorrhagic complications after treatment of cerebral aneurysms with the Pipeline Embolization Device. This study aimed to determine whether a last-recorded P2Y12 reaction units value of 60 or 240 predicts thromboembolic ...

Several studies have suggested a prominent (pro)inflammatory and harmful role of platelets in renal disease, and newer work has also demonstrated platelet release of proangiogenic factors. In the present study, we investigated the role of platelets in a mouse model of selective endothelial cell injury using either platelet depletion or the pharmacological P2Y12 receptor blocker clopidogrel as a...