Linked Life Data

20431852

Source:http://linkedlifedata.com/resource/pubmed/id/20431852

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-6-2
pubmed:abstractText
The thienopyridine P2Y12 receptor antagonists clopidogrel and prasugrel prevent arterial thrombosis and are routinely used following percutaneous coronary intervention. However, the optimal level of P2Y12 blockade to effectively inhibit platelet function is unknown. These studies utilised the active metabolite of prasugrel (R-138727) to achieve a range of P2Y12 blockade in vitro and assessed several aspects of platelet function. Blood from healthy volunteers was incubated with R-138727 (0-10 microM). P2Y12 receptor number was assessed using a 33P-2MeSADP binding assay. Platelet aggregation (PA) was measured by optical aggregometry with ADP 2-20 microM. VASP phosphorylation, annexin V binding, microparticle formation and P-selectin expression were assessed by flow cytometry. Increasing numbers of unblocked receptors were required for a sustained aggregation response with decreasing concentrations of ADP. A P2Y12 receptor blockade of 60-80% resulted in strong inhibition of final PA response, P-selectin expression, microparticle formation and vasodilator-stimulated phosphoprotein (VASP). PA induced by ADP 2 microM and P-selectin expression were particularly sensitive to low levels of receptor blockade whereas the VASP phosphorylation assay was relatively insensitive, requiring 60% receptor blockade to achieve substantial inhibition. Different assays varied in their ability to discriminate particular ranges of P2Y12 blockade and 80% or greater P2Y12 receptor blockade is required for consistently strong inhibition of several aspects of platelet function. These data guide the interpretation of results from different assays used to monitor the effects of P2Y12 receptor antagonists.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1210-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20431852-Adult, pubmed-meshheading:20431852-Anticoagulants, pubmed-meshheading:20431852-Blood Platelets, pubmed-meshheading:20431852-Cell Adhesion Molecules, pubmed-meshheading:20431852-Cell Separation, pubmed-meshheading:20431852-Cell-Derived Microparticles, pubmed-meshheading:20431852-Cells, Cultured, pubmed-meshheading:20431852-Coronary Thrombosis, pubmed-meshheading:20431852-Female, pubmed-meshheading:20431852-Flow Cytometry, pubmed-meshheading:20431852-Humans, pubmed-meshheading:20431852-Male, pubmed-meshheading:20431852-Microfilament Proteins, pubmed-meshheading:20431852-P-Selectin, pubmed-meshheading:20431852-Phosphoproteins, pubmed-meshheading:20431852-Piperazines, pubmed-meshheading:20431852-Platelet Activation, pubmed-meshheading:20431852-Radioligand Assay, pubmed-meshheading:20431852-Receptors, Purinergic P2, pubmed-meshheading:20431852-Receptors, Purinergic P2Y12, pubmed-meshheading:20431852-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
Relationship between degree of P2Y12 receptor blockade and inhibition of P2Y12-mediated platelet function.
pubmed:affiliation
Cardiovascular Science, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK. H.Judge@Sheffield.ac.uk
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't