Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease

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dc.contributor.authorFranca, Carolina N. [UNIFESP]
dc.contributor.authorPinheiro, Luiz F. M. [UNIFESP]
dc.contributor.authorIzar, Maria C. O. [UNIFESP]
dc.contributor.authorBrunialti, Milena K. C. [UNIFESP]
dc.contributor.authorSalomao, Reinaldo [UNIFESP]
dc.contributor.authorBianco, Henrique T. [UNIFESP]
dc.contributor.authorKasmas, Soraia H. [UNIFESP]
dc.contributor.authorBarbosa, Simone P. [UNIFESP]
dc.contributor.authorNucci, Gilberto de
dc.contributor.authorFonseca, Francisco A. H. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionNatl Inst Complex Fluids
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2016-01-24T14:17:57Z
dc.date.available2016-01-24T14:17:57Z
dc.date.issued2012-03-01
dc.description.abstractBackground: Increased numbers of endothelial (EMP) and platelet (PMP) microparticles have been related to cardiovascular risk factors and coronary artery disease. Little is known about the early effects of statins and clopidogrel on these new biomarkers of vascular homeostasis. the aim of the present study was to evaluate pharmacokinetic interactions between atorvastatin and clopidogrel and their effects, alone or combined, on EMP, PMP, and endothelial progenitor cells (EPC).Methods and Results: A prospective open-label study enrolled subjects with stable coronary disease (n=26). Drugs were given daily for 3 weeks (atorvastatin 80 mg, visits 1-3; clopidogrel 75 mg, visits 2-4). Counts of EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+), and pharmacokinetic parameters over 24 h were assessed at each visit. Atorvastatin plasma concentrations were increased by concomitant therapy with clopidogrel (maximum serum concentration [C-max], P=0.002; area under the clopidogrel or atorvastatin plasma concentration vs. time curve from 0 to the last detectable concentration [AUC(last)], P=0.03). After atorvastatin withdrawal there was an increase in clopidogrel plasma concentrations (C-max, P=0.009; AUC(last), P=0.039). PMP were inversely correlated with clopidogrel C. on visit 3 (rho=-0.57, P=0.006) and on visit 4 (rho=-0.54, P=0.01), and with clopidogrel AUC(last) on visit 3 (rho=-0.44, P=0.04), and on visit 4 (rho=-0.57, P=0.005). in addition, clopidogrel C-max was correlated with EPC (CD133+/KDR+) on visit 4 (rho=0.48, P=0.025). No correlations of atorvastatin and MP or EPC were found.Conclusions: the balance between platelet MP release and EPC mobilization seems influenced by clopidogrel plasma levels, suggesting a protective mechanism on coronary artery disease. (Circ J 2012; 76: 729-736)en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, BR-04039030 São Paulo, Brazil
dc.description.affiliationNatl Inst Complex Fluids, São Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Dept Pharmacol, Campinas, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, BR-04039030 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent729-736
dc.identifierhttp://dx.doi.org/10.1253/circj.CJ-11-1145
dc.identifier.citationCirculation Journal. Kyoto: Japanese Circulation Soc, v. 76, n. 3, p. 729-736, 2012.
dc.identifier.doi10.1253/circj.CJ-11-1145
dc.identifier.issn1346-9843
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34647
dc.identifier.wosWOS:000300922900034
dc.language.isoeng
dc.publisherJapanese Circulation Soc
dc.relation.ispartofCirculation Journal
dc.rightsAcesso aberto
dc.subjectClopidogrelen
dc.subjectEndothelial progenitor cellsen
dc.subjectPlateletsen
dc.subjectPharmacokineticsen
dc.subjectStatinen
dc.titleEndothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Diseaseen
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