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...
| Autor: | |
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| 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 |
| Sumario: | 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. |
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