La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica

Chronic kidney disease (CKD) is a global health problem that affects around 850 million people in the world. CKD is associated with the development of cardiac alterations that increase in more than 50% risk of mortality. In a previous study, it was demonstrated that during CKD progression, cardiac a...

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Detalles Bibliográficos
Autor: YADIRA ISABEL AMADOR MARTINEZ
Tipo de recurso: tesis de maestría
Estado:Versión publicada
Fecha de publicación:2020
País:México
Institución:Universidad Autónoma Metropolitana
Repositorio:Repositorio Institucional de la UAM Iztapalapa
Idioma:español
OAI Identifier:oai:bindani.izt.uam.mx:1v53jx20h
Acceso en línea:https://doi.org/10.24275/uami.1v53jx20h
Access Level:acceso abierto
Palabra clave:info:eu-repo/classification/LEM/Heart -- Fibrosis
info:eu-repo/classification/LEM/Insuficiencia cardiaca
info:eu-repo/classification/LEM/Inflammation
info:eu-repo/classification/LEM/Inflamación
info:eu-repo/classification/LEM/Biología experimental
info:eu-repo/classification/LEM/Heart failure
info:eu-repo/classification/LEM/Insuficiencia renal crónica
info:eu-repo/classification/LEM/Corazón -- Fibrosis
info:eu-repo/classification/LEM/Chronic renal failure
info:eu-repo/classification/LEM/Biology, Experimental
info:eu-repo/classification/cti/2
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repository_id_str
dc.title.none.fl_str_mv La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
title La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
spellingShingle La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
YADIRA ISABEL AMADOR MARTINEZ
info:eu-repo/classification/LEM/Heart -- Fibrosis
info:eu-repo/classification/LEM/Insuficiencia cardiaca
info:eu-repo/classification/LEM/Inflammation
info:eu-repo/classification/LEM/Inflamación
info:eu-repo/classification/LEM/Biología experimental
info:eu-repo/classification/LEM/Heart failure
info:eu-repo/classification/LEM/Insuficiencia renal crónica
info:eu-repo/classification/LEM/Corazón -- Fibrosis
info:eu-repo/classification/LEM/Chronic renal failure
info:eu-repo/classification/LEM/Biology, Experimental
info:eu-repo/classification/cti/2
title_short La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
title_full La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
title_fullStr La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
title_full_unstemmed La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
title_sort La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónica
dc.creator.none.fl_str_mv YADIRA ISABEL AMADOR MARTINEZ
author YADIRA ISABEL AMADOR MARTINEZ
author_facet YADIRA ISABEL AMADOR MARTINEZ
author_role author
dc.contributor.none.fl_str_mv JONATAN BARRERA CHIMAL
MARIO GARCIA LORENZANA
JULIO CESAR ALMANZA PEREZ
dc.subject.none.fl_str_mv info:eu-repo/classification/LEM/Heart -- Fibrosis
info:eu-repo/classification/LEM/Insuficiencia cardiaca
info:eu-repo/classification/LEM/Inflammation
info:eu-repo/classification/LEM/Inflamación
info:eu-repo/classification/LEM/Biología experimental
info:eu-repo/classification/LEM/Heart failure
info:eu-repo/classification/LEM/Insuficiencia renal crónica
info:eu-repo/classification/LEM/Corazón -- Fibrosis
info:eu-repo/classification/LEM/Chronic renal failure
info:eu-repo/classification/LEM/Biology, Experimental
info:eu-repo/classification/cti/2
topic info:eu-repo/classification/LEM/Heart -- Fibrosis
info:eu-repo/classification/LEM/Insuficiencia cardiaca
info:eu-repo/classification/LEM/Inflammation
info:eu-repo/classification/LEM/Inflamación
info:eu-repo/classification/LEM/Biología experimental
info:eu-repo/classification/LEM/Heart failure
info:eu-repo/classification/LEM/Insuficiencia renal crónica
info:eu-repo/classification/LEM/Corazón -- Fibrosis
info:eu-repo/classification/LEM/Chronic renal failure
info:eu-repo/classification/LEM/Biology, Experimental
info:eu-repo/classification/cti/2
description Chronic kidney disease (CKD) is a global health problem that affects around 850 million people in the world. CKD is associated with the development of cardiac alterations that increase in more than 50% risk of mortality. In a previous study, it was demonstrated that during CKD progression, cardiac alterations including hypertrophy, fibrosis, and myocardial dysfunction appear, and these events are related to the inac- tivation of the endothelial nitric oxide synthase (eNOS) in the heart. Because of that, in the first part of this research, we evaluated the effect of L-arginine administration, as an eNOS substrate for nitric oxide production, in the development of cardiovascu- lar alterations in a CKD model in male Wistar rats. We found that the cardiac altera- tions like hypertrophy, fibrosis, cardiac dysfunction, and eNOS inactivation in the heart were prevented when the animals were treated with L-arginine, suggesting that protection may be due to enhanced nitric oxide production in the heart. In the second part of this study, we focused on the cardiac inflammatory response during the early stages of CKD and its role on the emergence of chronic cardiac al- terations. We observed that during the early phase of CKD (72h and 120h), there was an increase in the infiltration of inflammatory cells like neutrophils, T lymphocytes, and dendritic cells. By depleting neutrophils in the early phase of CKD we showed that cardiac hypertrophy was reduced in the CKD animals. Next, we studied the pos- sible mechanisms involved in the increase of inflammatory infiltration in the heart dur- ing CKD and we found that during the early stages of CKD there was an increased expression of 54 genes related to inflammatory processes like immune system activation and interferon response. Finally, by evaluating epigenetic modifications in the hearts of CKD animals also in early stages, through bisulfite sequencing, it was found that in the initial phase of the CKD progression there were 104 differentially methylat- ed regions (DMRs) as compared with controls. The genes associated with DMRs in- cluded relevant genes to cardiac function maintenance and some that participate in the processes like regulation of cardiac metabolism and structure, pacemaker, and myocardial infarction risk. Taken together, our results show that early cardiac abnormalities such as infiltration of inflammatory cells, transcriptional, and epigenetic changes occur in an experi- mental CKD model and that these alterations can contribute to the development of chronic cardiovascular abnormalities in CKD. We also show that treatment with L- arginine prevents the development of chronic cardiac fibrosis and hypertrophy during CKD by promoting eNOS activation.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-18
dc.type.none.fl_str_mv info:eu-repo/semantics/masterThesis
info:eu-repo/semantics/publishedVersion
format masterThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.24275/uami.1v53jx20h
url https://doi.org/10.24275/uami.1v53jx20h
dc.language.none.fl_str_mv spa
language spa
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0
dc.source.none.fl_str_mv reponame:Repositorio Institucional de la UAM Iztapalapa
instname:Universidad Autónoma Metropolitana
instacron:UAM
instname_str Universidad Autónoma Metropolitana
instacron_str UAM
institution UAM
reponame_str Repositorio Institucional de la UAM Iztapalapa
collection Repositorio Institucional de la UAM Iztapalapa
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling La disfunción endotelial y la inflamación crónica como mecanismos en el desarrollo de fibrosis del miocardio durante la enfermedad renal crónicaYADIRA ISABEL AMADOR MARTINEZinfo:eu-repo/classification/LEM/Heart -- Fibrosisinfo:eu-repo/classification/LEM/Insuficiencia cardiacainfo:eu-repo/classification/LEM/Inflammationinfo:eu-repo/classification/LEM/Inflamacióninfo:eu-repo/classification/LEM/Biología experimentalinfo:eu-repo/classification/LEM/Heart failureinfo:eu-repo/classification/LEM/Insuficiencia renal crónicainfo:eu-repo/classification/LEM/Corazón -- Fibrosisinfo:eu-repo/classification/LEM/Chronic renal failureinfo:eu-repo/classification/LEM/Biology, Experimentalinfo:eu-repo/classification/cti/2Chronic kidney disease (CKD) is a global health problem that affects around 850 million people in the world. CKD is associated with the development of cardiac alterations that increase in more than 50% risk of mortality. In a previous study, it was demonstrated that during CKD progression, cardiac alterations including hypertrophy, fibrosis, and myocardial dysfunction appear, and these events are related to the inac- tivation of the endothelial nitric oxide synthase (eNOS) in the heart. Because of that, in the first part of this research, we evaluated the effect of L-arginine administration, as an eNOS substrate for nitric oxide production, in the development of cardiovascu- lar alterations in a CKD model in male Wistar rats. We found that the cardiac altera- tions like hypertrophy, fibrosis, cardiac dysfunction, and eNOS inactivation in the heart were prevented when the animals were treated with L-arginine, suggesting that protection may be due to enhanced nitric oxide production in the heart. In the second part of this study, we focused on the cardiac inflammatory response during the early stages of CKD and its role on the emergence of chronic cardiac al- terations. We observed that during the early phase of CKD (72h and 120h), there was an increase in the infiltration of inflammatory cells like neutrophils, T lymphocytes, and dendritic cells. By depleting neutrophils in the early phase of CKD we showed that cardiac hypertrophy was reduced in the CKD animals. Next, we studied the pos- sible mechanisms involved in the increase of inflammatory infiltration in the heart dur- ing CKD and we found that during the early stages of CKD there was an increased expression of 54 genes related to inflammatory processes like immune system activation and interferon response. Finally, by evaluating epigenetic modifications in the hearts of CKD animals also in early stages, through bisulfite sequencing, it was found that in the initial phase of the CKD progression there were 104 differentially methylat- ed regions (DMRs) as compared with controls. The genes associated with DMRs in- cluded relevant genes to cardiac function maintenance and some that participate in the processes like regulation of cardiac metabolism and structure, pacemaker, and myocardial infarction risk. Taken together, our results show that early cardiac abnormalities such as infiltration of inflammatory cells, transcriptional, and epigenetic changes occur in an experi- mental CKD model and that these alterations can contribute to the development of chronic cardiovascular abnormalities in CKD. We also show that treatment with L- arginine prevents the development of chronic cardiac fibrosis and hypertrophy during CKD by promoting eNOS activation.La enfermedad renal crónica (ERC) es un problema de salud global que afecta a cerca de 850 millones de personas en el mundo y además se asocia con el desarrollo de alteraciones cardiacas que incrementan en más del 50% el riesgo de mortalidad prematura en los pacientes. En estudios previos, se ha mostrado que durante la ERC se desarrolla hipertrofia, fibrosis y disfunción del miocardio acompañada de la inactivación de la sintasa de oxido nítrico endotelial (eNOS) a nivel cardiaco. Debido a esta problemática, en la primera parte de esta tesis se evaluó el efecto de la administración de L-arginina, como sustrato de la eNOS para la síntesis de óxido nítrico, sobre la aparición de alteraciones cardiovasculares en un modelo de ERC en ratas Wistar macho. Se encontró que algunas de las alteraciones cardiacas como hipertrofia, fibrosis y disfunción cardiaca así como la inactivación de la eNOS se previnieron cuando los animales con ERC fueron tratados con L-arginina. En la segunda parte de esta tesis, se hizo énfasis en el estudio de la respuesta inflamatoria en etapas tempranas de la ERC sobre la aparición de alteraciones crónicas en el corazón. Se observó que en la fase temprana (72 y 120 h) de la ERC hubo un incremento en la infiltración de células inflamatorias al corazón como neutrófilos, linfocitos T CD4 + y células dendríticas. Al eliminar a los neutrófilos en la fase temprana de la ERC se observó que la hipertrofia cardiaca disminuye en los animales con ERC. Al estudiar los posibles mecanismos involucrados en el incremento del infiltrado inflamatorio en el corazón durante la ERC, encontramos que en las etapas tempranas de la ERC, se incrementa la expresión de 54 genes viii relacionados a procesos de activación del sistema inmune y respuesta a interferón. Finalmente, al evaluar las modificaciones epigenéticas en los corazones de los animales con ERC igualmente en etapas tempranas, mediante secuenciación por bisulfito, se encontró que en la fase inicial de la progresión de la ERC hay 104 regiones metiladas diferencialmente (DMRs) comparado con los controles. Los genes asociados a DMRs incluyeron genes relevantes para la función cardiaca y que participan en procesos como la regulación de la estructura y metabolismo cardiaco, corrientes eléctricas del corazón y riesgo de infarto al miocardio. En conjunto, nuestros resultados muestran que en un modelo experimental de ERC se presentan alteraciones cardiacas tempranas como la infiltración de células inflamatorias, cambios transcripcionales y epigenéticos que pueden contribuir al desarrollo de alteraciones cardiovasculares crónicas en la ERC. Además mostramos que el tratamiento con L-arginina previene el desarrollo de fibrosis e hipertrofia cardiacas crónicas durante la ERC a través de promover la activación de la eNOS.JONATAN BARRERA CHIMALMARIO GARCIA LORENZANAJULIO CESAR ALMANZA PEREZ2020-12-18info:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.24275/uami.1v53jx20hreponame:Repositorio Institucional de la UAM Iztapalapainstname:Universidad Autónoma Metropolitanainstacron:UAMspainfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0oai:bindani.izt.uam.mx:1v53jx20h2025-11-26T19:19:14Z
score 15,812429

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