Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20613 |
Resumo: | Preeclampsia is the most common medical complication in pregnancy, accounting for the main cause of maternal and perinatal mortality and morbidity. Its etiology remains unknown which makes primary prevention difficult. It is a fact that gestation has a hemostatic imbalance with a tendency to hypercoagulability and an increased risk of thrombosis. These changes involve the purinergic signaling, which is composed of nucleotides and nucleosides, their respective receptors, and enzymes responsible for their degradation. During the inflammatory process, ATP, ADP, AMP and adenosine, which correlate directly with the activity of E-NTPDase, E-5'-nucleotidase, E- NPP and E-ADA. Adenine nucleotides may interact with purinergic receptors on the cell surface. The effects of extracellular ATP are controlled by the ectonucleotidases E-NTPDase and Ecto-5'-nucleotidase, which act on ATP and its degradation products, reducing its concentration in the medium and culminating in the production of adenosine, which acts as an immunomodulator or is converted to inosine by adenosine deaminase (E-ADA). Considering that hemostatic and inflammatory changes associated with normal pregnancy are more exacerbated in PE, it becomes relevant to study these mechanisms as a way of understanding the profile of this imbalance and act preventively. Therefore, the analysis of platelet parameters, as well as activity and expression of E-NTPDase and Ecto-5'nucleotidase were performed in 150 women divided into three groups: non-pregnant (n = 50), normotensive pregnant women (n = 50) and pregnant women with PE (n = 50). The results showed an increase of 74 (P < 0.001) and 72% (P < 0.01) in platelet aggregation in the addition of 5 μM and 10 μM, respectively, of adenosine diphosphate agonist (ADP); reduction of 19% (P < 0.05) of platelet count; 39% (P < 0.05) increase in immature platelet fraction (IPF); 7-fold increase (P < 0.001) in the E-ADA activity; reduction of 37 (P < 0.001) and 36% (P < 0.05) in the hydrolysis of ATP and ADP, respectively, and a correlation between platelet count, IPF, E-NTPDase and Ecto-5-'nucleotidase activity and expression in pregnant women with PE. Together, these results suggest that the endothelial dysfunction present in pregnant women with PE exacerbates the inflammatory and platelet aggregation mechanisms. The organism reacts to this inflammatory microenvironment through the reduced hydrolysis of ATP, with consequent platelet inhibition. However, this mechanism does not seem to be sufficient to overcome the disease since the disease is maintained. Therefore, the process of platelet aggregation as well as purinergic signaling seems to play an important role in the immune and inflammatory responses contributing to the clinical evolution of PE. Consequently, the evaluation of these parameters can lead to the development of protocols to prevent or treat this pathology effectively. |
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2021-04-16T21:21:38Z2021-04-16T21:21:38Z2018-08-28http://repositorio.ufsm.br/handle/1/20613Preeclampsia is the most common medical complication in pregnancy, accounting for the main cause of maternal and perinatal mortality and morbidity. Its etiology remains unknown which makes primary prevention difficult. It is a fact that gestation has a hemostatic imbalance with a tendency to hypercoagulability and an increased risk of thrombosis. These changes involve the purinergic signaling, which is composed of nucleotides and nucleosides, their respective receptors, and enzymes responsible for their degradation. During the inflammatory process, ATP, ADP, AMP and adenosine, which correlate directly with the activity of E-NTPDase, E-5'-nucleotidase, E- NPP and E-ADA. Adenine nucleotides may interact with purinergic receptors on the cell surface. The effects of extracellular ATP are controlled by the ectonucleotidases E-NTPDase and Ecto-5'-nucleotidase, which act on ATP and its degradation products, reducing its concentration in the medium and culminating in the production of adenosine, which acts as an immunomodulator or is converted to inosine by adenosine deaminase (E-ADA). Considering that hemostatic and inflammatory changes associated with normal pregnancy are more exacerbated in PE, it becomes relevant to study these mechanisms as a way of understanding the profile of this imbalance and act preventively. Therefore, the analysis of platelet parameters, as well as activity and expression of E-NTPDase and Ecto-5'nucleotidase were performed in 150 women divided into three groups: non-pregnant (n = 50), normotensive pregnant women (n = 50) and pregnant women with PE (n = 50). The results showed an increase of 74 (P < 0.001) and 72% (P < 0.01) in platelet aggregation in the addition of 5 μM and 10 μM, respectively, of adenosine diphosphate agonist (ADP); reduction of 19% (P < 0.05) of platelet count; 39% (P < 0.05) increase in immature platelet fraction (IPF); 7-fold increase (P < 0.001) in the E-ADA activity; reduction of 37 (P < 0.001) and 36% (P < 0.05) in the hydrolysis of ATP and ADP, respectively, and a correlation between platelet count, IPF, E-NTPDase and Ecto-5-'nucleotidase activity and expression in pregnant women with PE. Together, these results suggest that the endothelial dysfunction present in pregnant women with PE exacerbates the inflammatory and platelet aggregation mechanisms. The organism reacts to this inflammatory microenvironment through the reduced hydrolysis of ATP, with consequent platelet inhibition. However, this mechanism does not seem to be sufficient to overcome the disease since the disease is maintained. Therefore, the process of platelet aggregation as well as purinergic signaling seems to play an important role in the immune and inflammatory responses contributing to the clinical evolution of PE. Consequently, the evaluation of these parameters can lead to the development of protocols to prevent or treat this pathology effectively.A pré-eclâmpsia constitui-se na complicação médica mais encontrada na gravidez, sendo responsável pela principal causa da mortalidade e morbidade materna e perinatal. Sua etiologia ainda permanece desconhecida, o que dificulta a prevenção primária. Sabe-se que a gestação possui um desequilíbrio hemostático com tendência à hipercoagulabilidade e aumento do risco de trombose. Essas alterações envolvem a sinalização purinérgica, a qual é composta por nucleotídeos e nucleosídeos, seus respectivos receptores, além de enzimas responsáveis por sua degradação. Durante o processo inflamatório, dentre os mediadores capazes de modular as ações das plaquetas, destacam-se ATP, ADP, AMP e adenosina, os quais se correlacionam diretamente com a atividade das enzimas E-NTPDase, E-5’-nucleotidase, E-NPP e EADA. Os nucleotídeos da adenina podem interagir com receptores purinérgicos na superfície celular. Os efeitos do ATP extracelular são controlados pela ação das ectonucleotidases E-NTPDase e Ecto-5’- nucleotidase, que agem sobre o ATP e seus produtos de degradação, reduzindo sua concentração no meio e culminando na produção de adenosina, que atua como imunomodulador ou é convertida à inosina pela adenosina desaminase (E-ADA). Considerando que as alterações hemostáticas e inflamatórias associadas à gestação normal estão mais exacerbadas na PE torna-se relevante o estudo desses mecanismos como forma de entender o perfil desse desequilíbrio podendo atuar preventivamente. Sendo assim, realizou-se a análise de parâmetros plaquetários, assim como atividade e expressão da E-NTPDase e Ecto-5’nucleotidase em 150 mulheres divididas em três grupos: não-gestante (n = 50), gestante normotensa (n = 50) e gestante com PE (n = 50). Os resultados demonstraram um aumento de 74 (P < 0,001) e 72% (P < 0,01) da agregação plaquetária na adição de 5μM e 10μM, respectivamente, do agonista adenosina difosfato (ADP); redução de 19% (P < 0,05) da contagem de plaquetas; aumento de 39% (P < 0,05) do fração de plaquetas imaturas (IPF); aumento de 7 vezes (P < 0,001) na atividade da E-ADA; redução de 37 (P < 0,001) e 36% ( P < 0,05) na hidrólise do ATP e ADP, respectivamente e uma correlação entre contagem de plaquetas, IPF, atividade e expressão da E-NTPDase e da Ecto-5’-nucleotidase em gestantes com PE. Em conjunto, os resultados sugerem que a disfunção endotelial presente em gestantes com PE exacerba os mecanismos inflamatórios e de agregação plaquetária. O organismo tenta reagir frente a esse microambiente inflamatório através da hidrólise reduzida do ATP, com consequente inibição plaquetária. No entanto, esse mecanismo não parece ser suficiente, já que a doença é mantida. Portanto, o processo de agregação plaquetária assim como a sinalização purinérgica parece desempenhar um papel importante na resposta imune e inflamatória contribuindo para a evolução clínica da PE. Consequentemente a avaliação desses parâmetros podem levar ao desenvolvimento de protocolos para prevenir ou tratar essa patologia de forma eficaz.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilAnálises Clínicas e ToxicológicasAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessPré-eclâmpsiaPlaquetasFração de plaquetas imaturasSistema purinérgicoPreeclampsiaPlateletsFraction of immature plateletsPurinergic systemCNPQ::CIENCIAS DA SAUDE::FARMACIAAvaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsiaEvaluation of platelet index and activity of ntpdase and ecto-5'-nucleotidase in platelets of normotensive and preeclamptic pregnant womeninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSilva, José Edson Paz dahttp://lattes.cnpq.br/1177504021154172Leal, Daniela Bitencourt RosaRenner, Jane Dagmar PolloPavanato, Maria AmáliaBagatini, Margarete DulceChitolina, Maria Rosahttp://lattes.cnpq.br/0079826590014599Almeida, Taís Corrêa400300000005600600600600600600600600f31cbb2c-a6b3-42b5-99ec-4f7ceeff61497590cc54-1265-4230-b4f0-71d7d54a3bef273fd05e-83b4-4374-81a7-26d005e91f4b39b2240d-e328-442f-a918-42f4fb89416bf9c09a50-0698-4450-9e10-ac44830c8837273abd78-5b59-457d-b813-1eec64454b6a4c1ed42a-03f5-4ced-bf2d-b4bdcf46311creponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCF_2018_ALMEIDA_TAIS.pdfTES_PPGCF_2018_ALMEIDA_TAIS.pdfTeseapplication/pdf3493336http://repositorio.ufsm.br/bitstream/1/20613/1/TES_PPGCF_2018_ALMEIDA_TAIS.pdf611652988d6bac683f3c33963da3d871MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia |
dc.title.alternative.eng.fl_str_mv |
Evaluation of platelet index and activity of ntpdase and ecto-5'-nucleotidase in platelets of normotensive and preeclamptic pregnant women |
title |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia |
spellingShingle |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia Almeida, Taís Corrêa Pré-eclâmpsia Plaquetas Fração de plaquetas imaturas Sistema purinérgico Preeclampsia Platelets Fraction of immature platelets Purinergic system CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia |
title_full |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia |
title_fullStr |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia |
title_full_unstemmed |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia |
title_sort |
Avaliação dos índices plaquetários, atividade da e-ntpdase e da ecto-5'-nucleotidase em plaquetas de gestantes normotensas e com pré-eclâmpsia |
author |
Almeida, Taís Corrêa |
author_facet |
Almeida, Taís Corrêa |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Silva, José Edson Paz da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1177504021154172 |
dc.contributor.advisor-co1.fl_str_mv |
Leal, Daniela Bitencourt Rosa |
dc.contributor.referee1.fl_str_mv |
Renner, Jane Dagmar Pollo |
dc.contributor.referee2.fl_str_mv |
Pavanato, Maria Amália |
dc.contributor.referee3.fl_str_mv |
Bagatini, Margarete Dulce |
dc.contributor.referee4.fl_str_mv |
Chitolina, Maria Rosa |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0079826590014599 |
dc.contributor.author.fl_str_mv |
Almeida, Taís Corrêa |
contributor_str_mv |
Silva, José Edson Paz da Leal, Daniela Bitencourt Rosa Renner, Jane Dagmar Pollo Pavanato, Maria Amália Bagatini, Margarete Dulce Chitolina, Maria Rosa |
dc.subject.por.fl_str_mv |
Pré-eclâmpsia Plaquetas Fração de plaquetas imaturas Sistema purinérgico |
topic |
Pré-eclâmpsia Plaquetas Fração de plaquetas imaturas Sistema purinérgico Preeclampsia Platelets Fraction of immature platelets Purinergic system CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Preeclampsia Platelets Fraction of immature platelets Purinergic system |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Preeclampsia is the most common medical complication in pregnancy, accounting for the main cause of maternal and perinatal mortality and morbidity. Its etiology remains unknown which makes primary prevention difficult. It is a fact that gestation has a hemostatic imbalance with a tendency to hypercoagulability and an increased risk of thrombosis. These changes involve the purinergic signaling, which is composed of nucleotides and nucleosides, their respective receptors, and enzymes responsible for their degradation. During the inflammatory process, ATP, ADP, AMP and adenosine, which correlate directly with the activity of E-NTPDase, E-5'-nucleotidase, E- NPP and E-ADA. Adenine nucleotides may interact with purinergic receptors on the cell surface. The effects of extracellular ATP are controlled by the ectonucleotidases E-NTPDase and Ecto-5'-nucleotidase, which act on ATP and its degradation products, reducing its concentration in the medium and culminating in the production of adenosine, which acts as an immunomodulator or is converted to inosine by adenosine deaminase (E-ADA). Considering that hemostatic and inflammatory changes associated with normal pregnancy are more exacerbated in PE, it becomes relevant to study these mechanisms as a way of understanding the profile of this imbalance and act preventively. Therefore, the analysis of platelet parameters, as well as activity and expression of E-NTPDase and Ecto-5'nucleotidase were performed in 150 women divided into three groups: non-pregnant (n = 50), normotensive pregnant women (n = 50) and pregnant women with PE (n = 50). The results showed an increase of 74 (P < 0.001) and 72% (P < 0.01) in platelet aggregation in the addition of 5 μM and 10 μM, respectively, of adenosine diphosphate agonist (ADP); reduction of 19% (P < 0.05) of platelet count; 39% (P < 0.05) increase in immature platelet fraction (IPF); 7-fold increase (P < 0.001) in the E-ADA activity; reduction of 37 (P < 0.001) and 36% (P < 0.05) in the hydrolysis of ATP and ADP, respectively, and a correlation between platelet count, IPF, E-NTPDase and Ecto-5-'nucleotidase activity and expression in pregnant women with PE. Together, these results suggest that the endothelial dysfunction present in pregnant women with PE exacerbates the inflammatory and platelet aggregation mechanisms. The organism reacts to this inflammatory microenvironment through the reduced hydrolysis of ATP, with consequent platelet inhibition. However, this mechanism does not seem to be sufficient to overcome the disease since the disease is maintained. Therefore, the process of platelet aggregation as well as purinergic signaling seems to play an important role in the immune and inflammatory responses contributing to the clinical evolution of PE. Consequently, the evaluation of these parameters can lead to the development of protocols to prevent or treat this pathology effectively. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-08-28 |
dc.date.accessioned.fl_str_mv |
2021-04-16T21:21:38Z |
dc.date.available.fl_str_mv |
2021-04-16T21:21:38Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/20613 |
url |
http://repositorio.ufsm.br/handle/1/20613 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400300000005 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
f31cbb2c-a6b3-42b5-99ec-4f7ceeff6149 7590cc54-1265-4230-b4f0-71d7d54a3bef 273fd05e-83b4-4374-81a7-26d005e91f4b 39b2240d-e328-442f-a918-42f4fb89416b f9c09a50-0698-4450-9e10-ac44830c8837 273abd78-5b59-457d-b813-1eec64454b6a 4c1ed42a-03f5-4ced-bf2d-b4bdcf46311c |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Análises Clínicas e Toxicológicas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
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repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1801485295874473984 |