A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica
Autor(a) principal: | |
---|---|
Data de Publicação: | 2010 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/12596 |
Resumo: | The prevalence of obesity and metabolic syndrome (MS) is dramatically increasing in young people and becoming a public health problem in the majority of developed and developing countries. Both obesity and MS increase the number of patients exposed to the risk of cardiovascular disease. Recent studies have shown that a reduction in nitric oxide (NO) bioavailability is one of the major factors contributing to the deleterious action of insulin in the blood vessels of adult patients with obesity and MS. NO, a powerful vasodilator and platelet anti-aggregating agent, has the cationic amino acid L-arginine as a precursor, which is transported into platelets via transport system y+L. A family of enzymes known as NO sinthases (NOS) catalyses the oxidation of L-arginine in NO and L-citrulline and is composed of three isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS). The major objectives of this study are to investigate different steps of the L-arginine-NO pathway in platelets and their association with platelet aggregation, L-arginine plasma concentration, oxidative stress, and metabolic, hormonal, clinical and inflammatory markers in adolescent patients with obesity and MS. Thirty adolescents were included in this study: ten with obesity, ten with MS and ten healthy controls paired by age, sex and Tanner classification (controls: n= 10, 15.6 ± 0.7 years; obese: n= 10, 15 ± 0.9 years; MS: n= 10, 14.9 ± 0.8 years). Larginine transport (pmol/109cells/min) via system y+L was reduced in patients with MS (18.4 ± 3.8) and obesity (20.8 ± 4.7) compared to controls (52.3 ± 14.8). There was a positive correlation between L-arginine influx via system y+L and HDL-cholesterol. On the other hand, a negative correlation was found between L-arginine influx via system y+L and insulin levels, Homa-IR related to insulin resistance, Homa-Beta, related to betacell function and the leptin index. In relation to nitric oxide production, obesity and MS do not affect the activity and expression of NOS enzymes. The activity of superoxide dismutase (SOD), by measuring the inhibition of adrenaline autoxidation, showed a significant difference in platelets from patients with obesity (4235 ± 613,2nMol/mg protein) compared to controls (1011± 123,6 nmol/mg de protein) and MS (1713 ± 267,7 nmol/mg protein). At the systemic level, an activation of this anti-oxidant enzyme was also observed in the serum of patients with obesity and MS in relation to controls in the presence of similar levels of substances that are reactive to tiobarbituric acid (TBARS), a marker of lipid peroxidation. These results suggest that diminished L-arginine transport in platelets from adolescents with obesity and MS may be an early marker of platelet dysfunction. The alteration of this pathway correlates to insulin resistance and hyperinsulinemia. The contribution of this study and of factors that can be identified early may reduce cardiovascular risk during adult life in this population of patients. |
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Brunini, Tatiana Marlowe Cunhahttp://lattes.cnpq.br/1794383786839231Ribeiro, Antônio Cláudio Mendeshttp://lattes.cnpq.br/4764377589833985Carvalho, Jorge José dehttp://lattes.cnpq.br/2608779267915272Matos, Amélio Fernando de Godoyhttp://lattes.cnpq.br/4850752035210309Monteiro, Cláudia Bragahttp://lattes.cnpq.br/3258299174536231Moreira, Rodrigo de Oliveirahttp://lattes.cnpq.br/8313280775887526http://lattes.cnpq.br/2919422073568790Assumpção, Carmen Regina Leal de2021-01-06T20:52:47Z2011-04-252010-06-15ASSUMPÇÃO, Carmen Regina Leal de. A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica. 2010. 137 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2010.http://www.bdtd.uerj.br/handle/1/12596The prevalence of obesity and metabolic syndrome (MS) is dramatically increasing in young people and becoming a public health problem in the majority of developed and developing countries. Both obesity and MS increase the number of patients exposed to the risk of cardiovascular disease. Recent studies have shown that a reduction in nitric oxide (NO) bioavailability is one of the major factors contributing to the deleterious action of insulin in the blood vessels of adult patients with obesity and MS. NO, a powerful vasodilator and platelet anti-aggregating agent, has the cationic amino acid L-arginine as a precursor, which is transported into platelets via transport system y+L. A family of enzymes known as NO sinthases (NOS) catalyses the oxidation of L-arginine in NO and L-citrulline and is composed of three isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS). The major objectives of this study are to investigate different steps of the L-arginine-NO pathway in platelets and their association with platelet aggregation, L-arginine plasma concentration, oxidative stress, and metabolic, hormonal, clinical and inflammatory markers in adolescent patients with obesity and MS. Thirty adolescents were included in this study: ten with obesity, ten with MS and ten healthy controls paired by age, sex and Tanner classification (controls: n= 10, 15.6 ± 0.7 years; obese: n= 10, 15 ± 0.9 years; MS: n= 10, 14.9 ± 0.8 years). Larginine transport (pmol/109cells/min) via system y+L was reduced in patients with MS (18.4 ± 3.8) and obesity (20.8 ± 4.7) compared to controls (52.3 ± 14.8). There was a positive correlation between L-arginine influx via system y+L and HDL-cholesterol. On the other hand, a negative correlation was found between L-arginine influx via system y+L and insulin levels, Homa-IR related to insulin resistance, Homa-Beta, related to betacell function and the leptin index. In relation to nitric oxide production, obesity and MS do not affect the activity and expression of NOS enzymes. The activity of superoxide dismutase (SOD), by measuring the inhibition of adrenaline autoxidation, showed a significant difference in platelets from patients with obesity (4235 ± 613,2nMol/mg protein) compared to controls (1011± 123,6 nmol/mg de protein) and MS (1713 ± 267,7 nmol/mg protein). At the systemic level, an activation of this anti-oxidant enzyme was also observed in the serum of patients with obesity and MS in relation to controls in the presence of similar levels of substances that are reactive to tiobarbituric acid (TBARS), a marker of lipid peroxidation. These results suggest that diminished L-arginine transport in platelets from adolescents with obesity and MS may be an early marker of platelet dysfunction. The alteration of this pathway correlates to insulin resistance and hyperinsulinemia. The contribution of this study and of factors that can be identified early may reduce cardiovascular risk during adult life in this population of patients.A prevalência da obesidade e da síndrome metabólica (SM) vem aumentando dramaticamente em jovens e está se tornando um problema de saúde pública na maioria dos países desenvolvidos e em desenvolvimento. Tanto a obesidade quanto a SM aumentam o número de pacientes expostos ao risco de doença cardiovascular. Estudos recentes mostram que uma redução na biodisponipilidade de óxido nítrico (NO) é um dos principais fatores que contribui para a ação deletéria da insulina nos vasos de pacientes adultos com obesidade e SM. O NO, potente vasodilatador e anti-agregante plaquetário, tem como precursor o aminoácido catiônico L-arginina que é transportado para o interior das plaquetas através do carreador y+L. Uma família de enzimas denominadas NO sintases (NOS) catalisa a oxidação da L-arginina em NO e L-citrulina e é composta de três isoformas: neuronal (nNOS), induzível (iNOS) e endotelial (eNOS). Os objetivos principais do presente estudo são de investigar diferentes etapas da via L-arginina-NO em plaquetas associando agregação plaquetária, concentração plasmática de L-arginina, estresse oxidativo, marcadores metabólicos, hormonais, clínicos e inflamatórios em pacientes adolescentes com obesidade e SM. Foram incluídos no estudo trinta adolescentes, sendo dez com obesidade, dez com SM, e dez controles saudáveis pareados por idade, sexo e classificação de Tanner (controles: n= 10, 15.6 ± 0.7 anos; obesos: n= 10, 15 ± 0.9 anos; SM: n= 10, 14.9 ± 0.8 anos). O transporte de L-arginina (pmol/109céls/min) através do sistema y+L estava diminuído nos pacientes com SM (18.4 ± 3.8) e obesidade (20.8 ± 4.7), comparados aos controles (52.3 ± 14.8). Houve uma correlação positiva do influxo de L-arginina via sistema y+L com os níveis de HDL-Colesterol. Por outro lado, foi encontrada uma correlação negativa do influxo de L-arginina com os níveis de insulina, os índices Homa IR, relacionado a RI, Homa Beta, relacionado a função da célula beta e também com os índices de Leptina. Em relação a produção de NO, a obesidade e a SM não afetaram a atividade e expressão das enzimas NOS. A atividade da superóxido dismutase (SOD), através da mensuração da inibição da auto-oxidação da adrenalina, mostrou diferença significativa nas plaquetas de pacientes com obesidade (4235 ± 613,2 nMol/mg de proteína), quando comparada aos controles (1011± 123,6 nmol/mg de proteína) e SM (1713 ± 267,7 nmol/mg de proteína). A nível sistêmico, foi também evidenciada uma ativação desta enzima anti-oxidante no soro de pacientes obesos, em relação aos controles. A peroxidação lipídica avaliada pelas substâncias reativas ao ácido tiobarbitúrico (TBARS) estava inalterada no soro dos pacientes e controles. Estes resultados sugerem que o transporte de L-arginina diminuído nas plaquetas de adolescentes obesos e com SM pode ser um marcador precoce de disfunção plaquetária. A alteração desta via correlaciona-se com a resistência à insulina e hiperinsulinemia. A contribuição deste estudo e de fatores que possam ser precocemente identificados pode diminuir o risco cardiovascular na vida adulta desta população de pacientes.Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:52:47Z No. of bitstreams: 1 Tese - Carmen Assumpcao.pdf: 2941198 bytes, checksum: c24d223095071534ff0fcf22f8c32a56 (MD5)Made available in DSpace on 2021-01-06T20:52:47Z (GMT). No. of bitstreams: 1 Tese - Carmen Assumpcao.pdf: 2941198 bytes, checksum: c24d223095071534ff0fcf22f8c32a56 (MD5) Previous issue date: 2010-06-15application/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Fisiopatologia Clínica e ExperimentalUERJBRCentro Biomédico::Faculdade de Ciências MédicasObesityMetabolic SyndromePlateletNitric oxideL-arginineSystem y+LObesidadeSíndrome MetabólicaPlaquetaÓxido nítricoL-argininaSistema y+L.CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA CARDIORENALA via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólicaVia L-arginine-nitric oxide in platelets of adolescent obesity and metabolic syndromeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTese - Carmen Assumpcao.pdfapplication/pdf2941198http://www.bdtd.uerj.br/bitstream/1/12596/1/Tese+-+Carmen+Assumpcao.pdfc24d223095071534ff0fcf22f8c32a56MD511/125962024-02-26 16:36:42.521oai:www.bdtd.uerj.br:1/12596Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T19:36:42Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica |
dc.title.alternative.eng.fl_str_mv |
Via L-arginine-nitric oxide in platelets of adolescent obesity and metabolic syndrome |
title |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica |
spellingShingle |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica Assumpção, Carmen Regina Leal de Obesity Metabolic Syndrome Platelet Nitric oxide L-arginine System y+L Obesidade Síndrome Metabólica Plaqueta Óxido nítrico L-arginina Sistema y+L. CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA CARDIORENAL |
title_short |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica |
title_full |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica |
title_fullStr |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica |
title_full_unstemmed |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica |
title_sort |
A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica |
author |
Assumpção, Carmen Regina Leal de |
author_facet |
Assumpção, Carmen Regina Leal de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Brunini, Tatiana Marlowe Cunha |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1794383786839231 |
dc.contributor.advisor-co1.fl_str_mv |
Ribeiro, Antônio Cláudio Mendes |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/4764377589833985 |
dc.contributor.referee1.fl_str_mv |
Carvalho, Jorge José de |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/2608779267915272 |
dc.contributor.referee2.fl_str_mv |
Matos, Amélio Fernando de Godoy |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/4850752035210309 |
dc.contributor.referee3.fl_str_mv |
Monteiro, Cláudia Braga |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/3258299174536231 |
dc.contributor.referee4.fl_str_mv |
Moreira, Rodrigo de Oliveira |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/8313280775887526 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2919422073568790 |
dc.contributor.author.fl_str_mv |
Assumpção, Carmen Regina Leal de |
contributor_str_mv |
Brunini, Tatiana Marlowe Cunha Ribeiro, Antônio Cláudio Mendes Carvalho, Jorge José de Matos, Amélio Fernando de Godoy Monteiro, Cláudia Braga Moreira, Rodrigo de Oliveira |
dc.subject.eng.fl_str_mv |
Obesity Metabolic Syndrome Platelet Nitric oxide L-arginine System y+L |
topic |
Obesity Metabolic Syndrome Platelet Nitric oxide L-arginine System y+L Obesidade Síndrome Metabólica Plaqueta Óxido nítrico L-arginina Sistema y+L. CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA CARDIORENAL |
dc.subject.por.fl_str_mv |
Obesidade Síndrome Metabólica Plaqueta Óxido nítrico L-arginina Sistema y+L. |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA CARDIORENAL |
description |
The prevalence of obesity and metabolic syndrome (MS) is dramatically increasing in young people and becoming a public health problem in the majority of developed and developing countries. Both obesity and MS increase the number of patients exposed to the risk of cardiovascular disease. Recent studies have shown that a reduction in nitric oxide (NO) bioavailability is one of the major factors contributing to the deleterious action of insulin in the blood vessels of adult patients with obesity and MS. NO, a powerful vasodilator and platelet anti-aggregating agent, has the cationic amino acid L-arginine as a precursor, which is transported into platelets via transport system y+L. A family of enzymes known as NO sinthases (NOS) catalyses the oxidation of L-arginine in NO and L-citrulline and is composed of three isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS). The major objectives of this study are to investigate different steps of the L-arginine-NO pathway in platelets and their association with platelet aggregation, L-arginine plasma concentration, oxidative stress, and metabolic, hormonal, clinical and inflammatory markers in adolescent patients with obesity and MS. Thirty adolescents were included in this study: ten with obesity, ten with MS and ten healthy controls paired by age, sex and Tanner classification (controls: n= 10, 15.6 ± 0.7 years; obese: n= 10, 15 ± 0.9 years; MS: n= 10, 14.9 ± 0.8 years). Larginine transport (pmol/109cells/min) via system y+L was reduced in patients with MS (18.4 ± 3.8) and obesity (20.8 ± 4.7) compared to controls (52.3 ± 14.8). There was a positive correlation between L-arginine influx via system y+L and HDL-cholesterol. On the other hand, a negative correlation was found between L-arginine influx via system y+L and insulin levels, Homa-IR related to insulin resistance, Homa-Beta, related to betacell function and the leptin index. In relation to nitric oxide production, obesity and MS do not affect the activity and expression of NOS enzymes. The activity of superoxide dismutase (SOD), by measuring the inhibition of adrenaline autoxidation, showed a significant difference in platelets from patients with obesity (4235 ± 613,2nMol/mg protein) compared to controls (1011± 123,6 nmol/mg de protein) and MS (1713 ± 267,7 nmol/mg protein). At the systemic level, an activation of this anti-oxidant enzyme was also observed in the serum of patients with obesity and MS in relation to controls in the presence of similar levels of substances that are reactive to tiobarbituric acid (TBARS), a marker of lipid peroxidation. These results suggest that diminished L-arginine transport in platelets from adolescents with obesity and MS may be an early marker of platelet dysfunction. The alteration of this pathway correlates to insulin resistance and hyperinsulinemia. The contribution of this study and of factors that can be identified early may reduce cardiovascular risk during adult life in this population of patients. |
publishDate |
2010 |
dc.date.issued.fl_str_mv |
2010-06-15 |
dc.date.available.fl_str_mv |
2011-04-25 |
dc.date.accessioned.fl_str_mv |
2021-01-06T20:52:47Z |
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info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
ASSUMPÇÃO, Carmen Regina Leal de. A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica. 2010. 137 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2010. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/12596 |
identifier_str_mv |
ASSUMPÇÃO, Carmen Regina Leal de. A via L-arginina-óxido nítrico em plaquetas de adolescente com obesidade e síndrome metabólica. 2010. 137 f. Tese (Doutorado em Fisiopatologia Clínica e Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2010. |
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http://www.bdtd.uerj.br/handle/1/12596 |
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por |
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Universidade do Estado do Rio de Janeiro |
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Programa de Pós-Graduação em Fisiopatologia Clínica e Experimental |
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UERJ |
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BR |
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Centro Biomédico::Faculdade de Ciências Médicas |
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Universidade do Estado do Rio de Janeiro |
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