Implementación de un modelo en pez cebra (Danio rerio) de aterogénesis temprana inducido por dieta alta en grasa.
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Date
2024
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Publisher
Universidad de Concepción
Abstract
La enfermedad cardiovascular aterosclerótica es la principal causa de muerte a nivel nacional y global, es un proceso inflamatorio crónico marcado por la interacción de lipoproteínas, células inmunitarias y componentes celulares de la pared de los vasos sanguíneos. Un factor clave en el desarrollo de esta enfermedad es el aumento de lipoproteínas de baja densidad oxidadas (oxLDL), que promueven la disfunción endotelial y la formación de células espumosas, contribuyendo formación de estrías grasas, las cuales son el sello distintivo de aterosclerosis temprana. A pesar de que la aterosclerosis se desarrolla lenta y silenciosamente, hasta el día de hoy hay una ausencia de modelos experimentales adecuados para estudiar la enfermedad cardiovascular considerando su largo progreso, lo que dificulta estudiar los tratamientos para la aterosclerosis temprana y no permiten tener una idea clara de su complejidad in vivo, a lo largo de la vida de un individuo y en entorno fisiológico real. Por lo tanto, es necesario desarrollar en un modelo animal de aterosclerosis que permita comprender la patogénesis de la enfermedad desde sus inicios. En este contexto se evaluó el efecto de una dieta aterogénica a 4% (p/p) de colesterol sobre en larvas pez cebra (Danio reiro). En este modelo determinó el efecto el perfil bioquímico, la acumulación de lípidos en el sistema vascular y la respuesta inflamatoria localizada. Nuestros resultados muestran diferencias entre los peces alimentados con la dieta alta en colesterol y los controles, así se observó acumulación de lípido en la vasculatura, y una mayor cantidad de granulocitos localizados en la región perivascular, mayores concentraciones de las proteínas AST, TP, LDH, CRP. Además, se observa un aumento en los parámetros morfométricos y un mayor tamaño de gotas de lípido a nivel hepático. Estos resultados muestran que efectivamente el pez cebra desarrolla lesiones aterogénicas, inflamación y acumulación de células inflamatorias y permiten proponerlo como modelo para estudiar las etapas tempranas de la aterogénesis puede ser altamente valioso.
Atherosclerotic cardiovascular disease is the leading cause of mortality both nationally and globally. It represents a chronic inflammatory process characterized by the interaction of lipoproteins, immune cells, and cellular components of the vascular wall. A pivotal factor in developing this disease is the increase of oxidized low-density lipoproteins (ox-LDL), which promote endothelial dysfunction and the formation of foam cells, contributing to the development of fatty streaks, a hallmark of early-stage atherosclerosis. Despite the slow and silent progression of atherosclerosis, to date, there remains a lack of adequate experimental models to study cardiovascular disease given its prolonged progression, complicating the exploration of treatments for early atherosclerosis and obscuring a clear understanding of its complexity in vivo over an individual's lifetime and within an physiological context. Therefore, it is essential to develop an animal model of atherosclerosis that allows for an understanding of the disease's pathogenesis from its onset. In this context, we present a study involving the administration of a 4% (w/w) cholesterol atherogenic diet in zebrafish larvae (Danio rerio) due to several advantages compared to other models. We evaluated differences in the biochemical profile, lipid accumulation in the vascular system, and localized inflammatory response. Among the differences observed between fish fed the high-cholesterol diet and controls were increased lipid accumulation in the vasculature and a higher quantity of granulocytes localized in the perivascular region, elevated levels in the biochemical profile (AST, TP, LDH, CRP), increased ix morphometric parameters, and larger hepatic lipid droplets. These results demonstrate that zebrafish effectively develop indicators of atherogenic lesions and that their use as a model to study the early stages of atherogenesis can be highly valuable.
Atherosclerotic cardiovascular disease is the leading cause of mortality both nationally and globally. It represents a chronic inflammatory process characterized by the interaction of lipoproteins, immune cells, and cellular components of the vascular wall. A pivotal factor in developing this disease is the increase of oxidized low-density lipoproteins (ox-LDL), which promote endothelial dysfunction and the formation of foam cells, contributing to the development of fatty streaks, a hallmark of early-stage atherosclerosis. Despite the slow and silent progression of atherosclerosis, to date, there remains a lack of adequate experimental models to study cardiovascular disease given its prolonged progression, complicating the exploration of treatments for early atherosclerosis and obscuring a clear understanding of its complexity in vivo over an individual's lifetime and within an physiological context. Therefore, it is essential to develop an animal model of atherosclerosis that allows for an understanding of the disease's pathogenesis from its onset. In this context, we present a study involving the administration of a 4% (w/w) cholesterol atherogenic diet in zebrafish larvae (Danio rerio) due to several advantages compared to other models. We evaluated differences in the biochemical profile, lipid accumulation in the vascular system, and localized inflammatory response. Among the differences observed between fish fed the high-cholesterol diet and controls were increased lipid accumulation in the vasculature and a higher quantity of granulocytes localized in the perivascular region, elevated levels in the biochemical profile (AST, TP, LDH, CRP), increased ix morphometric parameters, and larger hepatic lipid droplets. These results demonstrate that zebrafish effectively develop indicators of atherogenic lesions and that their use as a model to study the early stages of atherogenesis can be highly valuable.
Description
Tesis presentada para optar al título de Bioquímico/a.
Keywords
Pez Cebra, Aterosclerosis, Dieta Alta en Grasa, Proteínas