Effects of Atorvastatin and T-786C Polymorphism of eNOS Gene on Plasma Metabolic Lipid Parameters

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorZAGO, Vanessa Helena de Souza
dc.contributor.authorSANTOS, Jose Eduardo Tanus dos
dc.contributor.authorDANELON, Mirian Regina Gardin
dc.contributor.authorSILVA, Roger Marcelo Mesquita da
dc.contributor.authorPANZOLDO, Natalia Baratella
dc.contributor.authorPARRA, Eliane Soler
dc.contributor.authorALEXANDRE, Fernanda
dc.contributor.authorVIRGINIO, Vitor Wilson de Moura
dc.contributor.authorQUINTAO, Eder Carlos Rocha
dc.contributor.authorFARIA, Eliana Cotta de
dc.date.accessioned2013-09-23T16:36:12Z
dc.date.available2013-09-23T16:36:12Z
dc.date.issued2013
dc.description.abstractBackground: Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. Objective: This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). Methods: Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. Results: The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12 +/- 7; CC, 22 +/- 12; p <= 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p <= 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p <= 0.07) and lipoprotein (a) (Lp(a)) (p <= 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. Conclusion: These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism. (Arq Bras Cardiol. 2013;100(1):14-20)
dc.description.abstractFUNDAMENTO: A atividade do óxido nítrico sintase endotelial (eNOS) pode ser modulada pelo colesterol da lipoproteína de alta densidade (HDL-C), estatinas ou polimorfismos, como o T-786C de eNOS. OBJETIVO: Este estudo teve como objetivo avaliar se o polimorfismo T-786C está associado a alterações nos efeitos da atorvastatina no perfil lipídico, nas concentrações de metabólitos de óxido nítrico (NO) e da proteína C reativa de alta sensibilidade (PCR-as). MÉTODOS: Trinta voluntários do sexo masculino, assintomáticos, com idade entre 18-56 anos foram genotipados e classificados de acordo com a ausência (TT, n = 15) ou presença (CC, n = 15) do polimorfismo. Eles foram selecionados aleatoriamente para a utilização de placebo e atorvastatina (10 mg/dia por 14 dias). Após cada tratamento foram medidos lípides, lipoproteínas, frações HDL2 e HDL3, atividade da proteína de transferência de colesteril éster (CETP), metabólitos de NO e PCR-as. RESULTADOS: As comparações entre genótipos após a administração de placebo mostraram aumento da atividade da CETP polimorfismo-dependente (TT, 12 ± 7; CC, 22 ± 12, p < 0,05). As análises da interação entre os tratamentos indicaram que a atorvastatina tem efeito sobre colesterol, LDL, nitrito e razões lípides/proteínas (HDL2 e HDL3) (p < 0,001) em ambos os genótipos. É interessante notar as interações genótipo/droga sobre a CETP (p < 0,07) e a lipoproteína (a) [Lp(a)] (p < 0,056), levando a uma diminuição limítrofe da CETP, embora sem afetar a Lp(a). A PRC-as não mostrou alterações. CONCLUSÃO: Os resultados sugerem que o tratamento com estatinas pode ser relevante para a prevenção primária da aterosclerose em pacientes com o polimorfismo T-786C do eNOS, considerando os efeitos no metabolismo lipídico.
dc.description.indexMEDLINE
dc.description.sponsorshipFAPESP (Foundation for Research Support of the State of Sao Paulo)
dc.description.sponsorshipCNPq (National Council for Scientific and Technological Development)
dc.description.sponsorshipFAPESP
dc.description.sponsorshipCNPq
dc.identifier.citationARQUIVOS BRASILEIROS DE CARDIOLOGIA, v.100, n.1, p.14-20, 2013
dc.identifier.doi10.1590/S0066-782X2012005000120
dc.identifier.issn0066-782X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1791
dc.language.isoeng
dc.language.isopor
dc.publisherARQUIVOS BRASILEIROS CARDIOLOGIA
dc.relation.ispartofArquivos Brasileiros de Cardiologia
dc.rightsopenAccess
dc.rights.holderCopyright ARQUIVOS BRASILEIROS CARDIOLOGIA
dc.subjectLipid Metabolism
dc.subjectPolymorphism, Genetic
dc.subjectLipid Regulating Agents
dc.subjectNitric Oxide
dc.subjectProtein C
dc.subjectMetabolismo dos Lipídeos
dc.subjectPolimorfismo Genético
dc.subjectReguladores do Metabolismo de Lipídeos
dc.subjectÓxido Nítrico
dc.subjectProteína C
dc.subject.othernitric-oxide synthase
dc.subject.othercholesteryl ester transfer
dc.subject.otherhigh-density-lipoprotein
dc.subject.othercoronary-artery-disease
dc.subject.otherc-reactive protein
dc.subject.otherendothelial function
dc.subject.other5'-flanking region
dc.subject.otherhdl-cholesterol
dc.subject.othershear-stress
dc.subject.otherstatins
dc.subject.wosCardiac & Cardiovascular Systems
dc.titleEffects of Atorvastatin and T-786C Polymorphism of eNOS Gene on Plasma Metabolic Lipid Parameters
dc.title.alternativeEfeitos da atorvastatina e do polimorfismo T-786C do gene eNOS sobre parâmetros do metabolismo lipídico plasmático
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalZAGO, Vanessa Helena de Souza:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.author.externalSANTOS, Jose Eduardo Tanus dos:Univ Sao Paulo, Fac Ciencias Med, Dept Farmacol, BR-14049 Ribeirao Preto, Brazil
hcfmusp.author.externalDANELON, Mirian Regina Gardin:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.author.externalSILVA, Roger Marcelo Mesquita da:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.author.externalPANZOLDO, Natalia Baratella:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.author.externalPARRA, Eliane Soler:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.author.externalALEXANDRE, Fernanda:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.author.externalVIRGINIO, Vitor Wilson de Moura:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.author.externalFARIA, Eliana Cotta de:Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, Lab Lipides Nucl Med & Cirurgia Expt, Campinas, SP, Brazil; Univ Sao Paulo, Fac Ciencias Med, Lab Lipides LIM10, Sao Paulo, Brazil
hcfmusp.citation.scopus6
hcfmusp.contributor.author-fmusphcEDER CARLOS ROCHA QUINTAO
hcfmusp.description.beginpage14
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hcfmusp.description.issue1
hcfmusp.description.volume100
hcfmusp.origemWOS
hcfmusp.origem.pubmed23250834
hcfmusp.origem.scieloSCIELO:S0066-782X2013000100004
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hcfmusp.origem.wosWOS:000316124400009
hcfmusp.publisher.cityRIO DE JANEIRO
hcfmusp.publisher.countryBRAZIL
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
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