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

Detalhes bibliográficos
Autor(a) principal: Franca, Carolina N. [UNIFESP]
Data de Publicação: 2012
Outros Autores: Pinheiro, Luiz F. M. [UNIFESP], Izar, Maria C. O. [UNIFESP], Brunialti, Milena K. C. [UNIFESP], Salomao, Reinaldo [UNIFESP], Bianco, Henrique T. [UNIFESP], Kasmas, Soraia H. [UNIFESP], Barbosa, Simone P. [UNIFESP], Nucci, Gilberto de, Fonseca, Francisco A. H. [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/001300000x86r
Texto Completo: http://dx.doi.org/10.1253/circj.CJ-11-1145
http://repositorio.unifesp.br/handle/11600/34647
Resumo: Background: 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)
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spelling Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery DiseaseClopidogrelEndothelial progenitor cellsPlateletsPharmacokineticsStatinBackground: 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)Universidade Federal de São Paulo, Dept Med, BR-04039030 São Paulo, BrazilNatl Inst Complex Fluids, São Paulo, BrazilUniv Estadual Campinas, Dept Pharmacol, Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Med, BR-04039030 São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Japanese Circulation SocUniversidade Federal de São Paulo (UNIFESP)Natl Inst Complex FluidsUniversidade Estadual de Campinas (UNICAMP)Franca, Carolina N. [UNIFESP]Pinheiro, Luiz F. M. [UNIFESP]Izar, Maria C. O. [UNIFESP]Brunialti, Milena K. C. [UNIFESP]Salomao, Reinaldo [UNIFESP]Bianco, Henrique T. [UNIFESP]Kasmas, Soraia H. [UNIFESP]Barbosa, Simone P. [UNIFESP]Nucci, Gilberto deFonseca, Francisco A. H. [UNIFESP]2016-01-24T14:17:57Z2016-01-24T14:17:57Z2012-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion729-736http://dx.doi.org/10.1253/circj.CJ-11-1145Circulation Journal. Kyoto: Japanese Circulation Soc, v. 76, n. 3, p. 729-736, 2012.10.1253/circj.CJ-11-11451346-9843http://repositorio.unifesp.br/handle/11600/34647WOS:000300922900034ark:/48912/001300000x86rengCirculation Journalinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2016-01-24T12:17:57Zoai:repositorio.unifesp.br/:11600/34647Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:43:01.274825Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
title Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
spellingShingle Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
Franca, Carolina N. [UNIFESP]
Clopidogrel
Endothelial progenitor cells
Platelets
Pharmacokinetics
Statin
title_short Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
title_full Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
title_fullStr Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
title_full_unstemmed Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
title_sort Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
author Franca, Carolina N. [UNIFESP]
author_facet Franca, Carolina N. [UNIFESP]
Pinheiro, Luiz F. M. [UNIFESP]
Izar, Maria C. O. [UNIFESP]
Brunialti, Milena K. C. [UNIFESP]
Salomao, Reinaldo [UNIFESP]
Bianco, Henrique T. [UNIFESP]
Kasmas, Soraia H. [UNIFESP]
Barbosa, Simone P. [UNIFESP]
Nucci, Gilberto de
Fonseca, Francisco A. H. [UNIFESP]
author_role author
author2 Pinheiro, Luiz F. M. [UNIFESP]
Izar, Maria C. O. [UNIFESP]
Brunialti, Milena K. C. [UNIFESP]
Salomao, Reinaldo [UNIFESP]
Bianco, Henrique T. [UNIFESP]
Kasmas, Soraia H. [UNIFESP]
Barbosa, Simone P. [UNIFESP]
Nucci, Gilberto de
Fonseca, Francisco A. H. [UNIFESP]
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
Natl Inst Complex Fluids
Universidade Estadual de Campinas (UNICAMP)
dc.contributor.author.fl_str_mv Franca, Carolina N. [UNIFESP]
Pinheiro, Luiz F. M. [UNIFESP]
Izar, Maria C. O. [UNIFESP]
Brunialti, Milena K. C. [UNIFESP]
Salomao, Reinaldo [UNIFESP]
Bianco, Henrique T. [UNIFESP]
Kasmas, Soraia H. [UNIFESP]
Barbosa, Simone P. [UNIFESP]
Nucci, Gilberto de
Fonseca, Francisco A. H. [UNIFESP]
dc.subject.por.fl_str_mv Clopidogrel
Endothelial progenitor cells
Platelets
Pharmacokinetics
Statin
topic Clopidogrel
Endothelial progenitor cells
Platelets
Pharmacokinetics
Statin
description Background: 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)
publishDate 2012
dc.date.none.fl_str_mv 2012-03-01
2016-01-24T14:17:57Z
2016-01-24T14:17:57Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1253/circj.CJ-11-1145
Circulation Journal. Kyoto: Japanese Circulation Soc, v. 76, n. 3, p. 729-736, 2012.
10.1253/circj.CJ-11-1145
1346-9843
http://repositorio.unifesp.br/handle/11600/34647
WOS:000300922900034
dc.identifier.dark.fl_str_mv ark:/48912/001300000x86r
url http://dx.doi.org/10.1253/circj.CJ-11-1145
http://repositorio.unifesp.br/handle/11600/34647
identifier_str_mv Circulation Journal. Kyoto: Japanese Circulation Soc, v. 76, n. 3, p. 729-736, 2012.
10.1253/circj.CJ-11-1145
1346-9843
WOS:000300922900034
ark:/48912/001300000x86r
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Circulation Journal
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 729-736
dc.publisher.none.fl_str_mv Japanese Circulation Soc
publisher.none.fl_str_mv Japanese Circulation Soc
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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