Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , , |
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) |
id |
UFSP_e6d8dfd2b11512eed1982857faab6459 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br/:11600/34647 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
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 |
_version_ |
1818602532907253760 |