eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity

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dc.contributor.authorNagassaki, S.
dc.contributor.authorHerculano, R. D.
dc.contributor.authorGraeff, Carlos Frederico de Oliveira [UNESP]
dc.contributor.authorTanus-Santos, J. E.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T13:26:16Z
dc.date.available2014-05-20T13:26:16Z
dc.date.issued2009-04-01
dc.description.abstractStatins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the fluidity of erythrocyte membranes.We genotyped 200 healthy subjects (males, 18-60 years of age) and then randomly selected 15 of these with the TT genotype and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined in the erythrocytes.Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations were found in the CC subjects than in the TT subjects (P < 0.05).These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes.en
dc.description.affiliationUniv São Paulo, Fac Med Ribeirao Preto, Dept Farmacol, BR-14049900 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniv São Paulo, Fac Filosofia Ciencias & Letras Ribeirao Pret, Dept Fis & Matemat, BR-14040901 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, Fac Ciencias Bauru, Dept Fis, BR-17033360 Bauru, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Fac Ciencias Bauru, Dept Fis, BR-17033360 Bauru, SP, Brazil
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.extent385-392
dc.identifierhttp://dx.doi.org/10.1007/s00228-008-0602-7
dc.identifier.citationEuropean Journal of Clinical Pharmacology. New York: Springer, v. 65, n. 4, p. 385-392, 2009.
dc.identifier.doi10.1007/s00228-008-0602-7
dc.identifier.issn0031-6970
dc.identifier.orcid0000-0003-0162-8273
dc.identifier.urihttp://hdl.handle.net/11449/8438
dc.identifier.wosWOS:000264176100007
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofEuropean Journal of Clinical Pharmacology
dc.relation.ispartofjcr2.679
dc.relation.ispartofsjr1,159
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectEndothelial nitric oxide synthaseen
dc.subjectEPRen
dc.subjectGenotypesen
dc.subjectNitric oxideen
dc.subjectPolymorphismsen
dc.subjectStatinsen
dc.titleeNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidityen
dc.typeArtigo
dcterms.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dcterms.rightsHolderSpringer
unesp.author.lattes5268607684223281[3]
unesp.author.orcid0000-0003-0162-8273[3]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências, Baurupt
unesp.departmentFísica - FCpt

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