Estudios científicos

Myricetin ameliorates atherosclerosis in the low-density-lipoprotein receptor knockout mice by suppression of cholesterol accumulation in macrophage foam cells

Abstract:

BACKGROUND:
Myricetin, a major flavonoid found in several foods including berries, grapes and wine, exhibited strong antioxidant potency, yet the effect on atherosclerosis is not fully understood. In this study, we examined the effect of myricetin on lipid accumulation in macrophage and atherosclerosis in atherosclerosis-prone low density lipoprotein receptor-deficient (Ldlr -/- ) mice.
METHODS:
Ldlr -/- mice were fed an atherogenic diet supplemented with myricetin (0.15% in the diet, v/v) for 8 weeks. Body weight, adipose tissue weight, food intake, serum biochemical parameters were measured. Atherosclerosis lesions and macrophages accumulaton in lesions were analyzed and quantified. Macrophages were exposed to 20 μM of myricetin before incubated with oxidized low-density lipoprotein (ox-LDL) (25μg/mL) or Dil-ox-LDL for the indicated time. Lipid uptake and foam cell formation were evaluated by flow cytometry and microscopy. The intracellular lipids were extracted and measured. mRNA expression and protein of cholesterol metabolism related receptors were analyzed.
RESULTS:
Myricetin administration reduced the weight, plasma lipid levels but not food intake in Ldlr -/- mice when fed an atherogenic diet. Myceritin-treated Ldlr -/- mice displayed significantly less atherosclerotic areas and macrophages in the cross sections of the aortic root. There were also less lipophilic areas in En face Oil red O staining of aorta from myceritin-treated Ldlr -/- mice. Myceritin treatment also markedly ameliorated ox-LDL-induced cholesterol accumulation in macrophages. The expression of CD36 were decreased in myricetin treated macrophages with ox-LDL incubation, while scavenger receptors class A (SR-A) and scavenger receptors class B (SR-BI) expression was not altered, indicating that these effect of myricetin were dependent on CD36 pathway.
CONCLUSIONS:
Our findings indicated that myricetin suppressed cholesterol accumulation in macrophage foam cells by inhibition of CD36-mediated ox-LDL uptake, and suggested myricetin may have an important therapeutic function for atherosclerosis.

Comentarios divulgativos:

La miricetina es un compuesto flavonoide que está presente en los frutos rojos, las uvas y el vino y que se caracteriza por su capacidad antioxidante. En este estudio los investigadores valoran su efecto sobre la aterosclerosis, y más concretamente sobre la acumulación lipídica de los macrófagos, en un modelo animal deficiente en el receptor de las lipoproteínas de baja densidad (LDL), al cual se suministró una dieta aterogénica suplementada con miricetina durante 8 semanas.

Los resultados mostraron que la suplementación con miricetina se asociaba a un menor peso de los animales y con menores concentraciones de lípidos plasmáticos, sin embargo, no se observaban cambios significativos en la ingesta. Estos animales también presentaban una menor presencia de placas ateroscleróticas y de macrófagos en la aorta. Los macrófagos de los animales suplementados con miricetina acumulaban menores cantidades de colesterol en presencia de LDL oxidadas y mostraban una menor expresión de CD36, una proteína asociada a procesos de adhesión celular. De modo que la miricetina podría tener un papel en el tratamiento de la aterosclerosis, al reducir el acúmulo de colesterol por parte de las células espumosas vía inhibición del CD36.