Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1475-2840-11-5 http://hdl.handle.net/11449/20904 |
Resumo: | c Background: Adiposity greatly increases the risk of atherothrombotic events, a pathological condition where a chronic state of oxidative stress is reported to play a major role. This study aimed to investigate the involvement of (NO)-soluble guanylyl cyclase (sGC) signaling pathway in the platelet dysfunction from high fat-fed (HFF) rats.Methods: Male Wistar rats were fed for 10 weeks with standard chow (SCD) or high-fat diet (HFD). ADP (10 mu M)-and thrombin (100 mU/ml)-induced washed platelet aggregation were evaluated. Measurement of intracellular levels of ROS levels was carried out using flow cytometry. Cyclic GMP levels were evaluated using ELISA kits.Results: High-fat fed rats exhibited significant increases in body weight, epididymal fat, fasting glucose levels and glucose intolerance compared with SCD group. Platelet aggregation induced by ADP (n = 8) and thrombin from HFD rats (n = 8) were significantly greater (P < 0.05) compared with SCD group. Platelet activation with ADP increased by 54% the intraplatelet ROS production in HFD group, as measured by flow cytometry (n = 6). N-acetylcysteine (NAC; 1 mM) and PEG-catalase (1000 U/ml) fully prevented the increased ROS production and platelet hyperaggregability in HFD group. The NO donors sodium nitroprusside (SNP; 10 mu M) and SNAP (10 mu M), as well as the NO-independent soluble guanylyl cyclase stimulator BAY 41-2272 (10 mu M) inhibited the platelet aggregation in HFD group with lower efficacy (P < 0.05) compared with SCD group. The cGMP levels in response to these agents were also markedly lower in HFD group (P < 0.05). The prostacyclin analogue iloprost (1 mu M) reduced platelet aggregation in HFD and SCD rats in a similar fashion (n = 4).Conclusions: Metabolic abnormalities as consequence of HFD cause platelet hyperaggregability involving enhanced intraplatelet ROS production and decreased NO bioavailability that appear to be accompanied by potential defects in the prosthetic haem group of soluble guanylyl cyclase. |
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Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species productionPlatelet aggregationObesityReactive-oxygen speciesNitric oxideCyclic GMPBAY 41-2272c Background: Adiposity greatly increases the risk of atherothrombotic events, a pathological condition where a chronic state of oxidative stress is reported to play a major role. This study aimed to investigate the involvement of (NO)-soluble guanylyl cyclase (sGC) signaling pathway in the platelet dysfunction from high fat-fed (HFF) rats.Methods: Male Wistar rats were fed for 10 weeks with standard chow (SCD) or high-fat diet (HFD). ADP (10 mu M)-and thrombin (100 mU/ml)-induced washed platelet aggregation were evaluated. Measurement of intracellular levels of ROS levels was carried out using flow cytometry. Cyclic GMP levels were evaluated using ELISA kits.Results: High-fat fed rats exhibited significant increases in body weight, epididymal fat, fasting glucose levels and glucose intolerance compared with SCD group. Platelet aggregation induced by ADP (n = 8) and thrombin from HFD rats (n = 8) were significantly greater (P < 0.05) compared with SCD group. Platelet activation with ADP increased by 54% the intraplatelet ROS production in HFD group, as measured by flow cytometry (n = 6). N-acetylcysteine (NAC; 1 mM) and PEG-catalase (1000 U/ml) fully prevented the increased ROS production and platelet hyperaggregability in HFD group. The NO donors sodium nitroprusside (SNP; 10 mu M) and SNAP (10 mu M), as well as the NO-independent soluble guanylyl cyclase stimulator BAY 41-2272 (10 mu M) inhibited the platelet aggregation in HFD group with lower efficacy (P < 0.05) compared with SCD group. The cGMP levels in response to these agents were also markedly lower in HFD group (P < 0.05). The prostacyclin analogue iloprost (1 mu M) reduced platelet aggregation in HFD and SCD rats in a similar fashion (n = 4).Conclusions: Metabolic abnormalities as consequence of HFD cause platelet hyperaggregability involving enhanced intraplatelet ROS production and decreased NO bioavailability that appear to be accompanied by potential defects in the prosthetic haem group of soluble guanylyl cyclase.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, São Paulo, BrazilUniv Estadual Paulista, Inst Biosci, Dept Phys Educ, São Paulo, BrazilUniv Estadual Paulista, Inst Biosci, Dept Phys Educ, São Paulo, BrazilBiomed Central Ltd.Universidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Monteiro, Priscila F.Morganti, Rafael P.Delbin, Maria A. [UNESP]Calixto, Marina C.Lopes-Pires, Maria E.Marcondes, SisiZanesco, Angelina [UNESP]Antunes, Edson2013-09-30T18:49:27Z2014-05-20T13:58:50Z2013-09-30T18:49:27Z2014-05-20T13:58:50Z2012-01-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://dx.doi.org/10.1186/1475-2840-11-5Cardiovascular Diabetology. London: Biomed Central Ltd., v. 11, p. 9, 2012.1475-2840http://hdl.handle.net/11449/2090410.1186/1475-2840-11-5WOS:000302474500001WOS000302474500001.pdf4472007237545596Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCardiovascular Diabetology5.2352,157info:eu-repo/semantics/openAccess2024-10-21T14:31:17Zoai:repositorio.unesp.br:11449/20904Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-10-21T14:31:17Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production |
title |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production |
spellingShingle |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production Monteiro, Priscila F. Platelet aggregation Obesity Reactive-oxygen species Nitric oxide Cyclic GMP BAY 41-2272 |
title_short |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production |
title_full |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production |
title_fullStr |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production |
title_full_unstemmed |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production |
title_sort |
Platelet hyperaggregability in high-fat fed rats: A role for intraplatelet reactive-oxygen species production |
author |
Monteiro, Priscila F. |
author_facet |
Monteiro, Priscila F. Morganti, Rafael P. Delbin, Maria A. [UNESP] Calixto, Marina C. Lopes-Pires, Maria E. Marcondes, Sisi Zanesco, Angelina [UNESP] Antunes, Edson |
author_role |
author |
author2 |
Morganti, Rafael P. Delbin, Maria A. [UNESP] Calixto, Marina C. Lopes-Pires, Maria E. Marcondes, Sisi Zanesco, Angelina [UNESP] Antunes, Edson |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Monteiro, Priscila F. Morganti, Rafael P. Delbin, Maria A. [UNESP] Calixto, Marina C. Lopes-Pires, Maria E. Marcondes, Sisi Zanesco, Angelina [UNESP] Antunes, Edson |
dc.subject.por.fl_str_mv |
Platelet aggregation Obesity Reactive-oxygen species Nitric oxide Cyclic GMP BAY 41-2272 |
topic |
Platelet aggregation Obesity Reactive-oxygen species Nitric oxide Cyclic GMP BAY 41-2272 |
description |
c Background: Adiposity greatly increases the risk of atherothrombotic events, a pathological condition where a chronic state of oxidative stress is reported to play a major role. This study aimed to investigate the involvement of (NO)-soluble guanylyl cyclase (sGC) signaling pathway in the platelet dysfunction from high fat-fed (HFF) rats.Methods: Male Wistar rats were fed for 10 weeks with standard chow (SCD) or high-fat diet (HFD). ADP (10 mu M)-and thrombin (100 mU/ml)-induced washed platelet aggregation were evaluated. Measurement of intracellular levels of ROS levels was carried out using flow cytometry. Cyclic GMP levels were evaluated using ELISA kits.Results: High-fat fed rats exhibited significant increases in body weight, epididymal fat, fasting glucose levels and glucose intolerance compared with SCD group. Platelet aggregation induced by ADP (n = 8) and thrombin from HFD rats (n = 8) were significantly greater (P < 0.05) compared with SCD group. Platelet activation with ADP increased by 54% the intraplatelet ROS production in HFD group, as measured by flow cytometry (n = 6). N-acetylcysteine (NAC; 1 mM) and PEG-catalase (1000 U/ml) fully prevented the increased ROS production and platelet hyperaggregability in HFD group. The NO donors sodium nitroprusside (SNP; 10 mu M) and SNAP (10 mu M), as well as the NO-independent soluble guanylyl cyclase stimulator BAY 41-2272 (10 mu M) inhibited the platelet aggregation in HFD group with lower efficacy (P < 0.05) compared with SCD group. The cGMP levels in response to these agents were also markedly lower in HFD group (P < 0.05). The prostacyclin analogue iloprost (1 mu M) reduced platelet aggregation in HFD and SCD rats in a similar fashion (n = 4).Conclusions: Metabolic abnormalities as consequence of HFD cause platelet hyperaggregability involving enhanced intraplatelet ROS production and decreased NO bioavailability that appear to be accompanied by potential defects in the prosthetic haem group of soluble guanylyl cyclase. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-01-16 2013-09-30T18:49:27Z 2013-09-30T18:49:27Z 2014-05-20T13:58:50Z 2014-05-20T13:58:50Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1475-2840-11-5 Cardiovascular Diabetology. London: Biomed Central Ltd., v. 11, p. 9, 2012. 1475-2840 http://hdl.handle.net/11449/20904 10.1186/1475-2840-11-5 WOS:000302474500001 WOS000302474500001.pdf 4472007237545596 |
url |
http://dx.doi.org/10.1186/1475-2840-11-5 http://hdl.handle.net/11449/20904 |
identifier_str_mv |
Cardiovascular Diabetology. London: Biomed Central Ltd., v. 11, p. 9, 2012. 1475-2840 10.1186/1475-2840-11-5 WOS:000302474500001 WOS000302474500001.pdf 4472007237545596 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cardiovascular Diabetology 5.235 2,157 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
9 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd. |
publisher.none.fl_str_mv |
Biomed Central Ltd. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
_version_ |
1826304652887457792 |