File:The Anti-atherogenic Role of Exercise Is Associated With the Attenuation of Bone Marrow-Derived Macrophage Activation and Migration in Hypercholesterolemic Mice.jpg
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English: An early event in atherogenesis is the recruitment and infiltration of circulating monocytes and macrophage activation in the subendothelial space. Atherosclerosis subsequently progresses as a unresolved inflammatory disease, particularly in hypercholesterolemic conditions. Although physical exercise training has been a widely accepted strategy to inhibit atherosclerosis, its impact on arterial wall inflammation and macrophage phenotype and function has not yet been directly evaluated. Thus, the aim of this study was to investigate the effects of aerobic exercise training on the inflammatory state of atherosclerotic lesions with a focus on macrophages. Hypercholesterolemic LDL-receptor-deficient male mice were subjected to treadmill training for 8 weeks and fed a high-fat diet. Analyses included plasma lipoprotein and cytokine levels; aortic root staining for lipids (oil red O); macrophages (CD68, MCP1 and IL1β); oxidative (nitrotyrosine and, DHE) and endoplasmic reticulum (GADD) stress markers. Primary bone marrow-derived macrophages (BMDM) were assayed for migration activity, motility phenotype (Rac1 and F-actin) and inflammation-related gene expression. Plasma levels of HDL cholesterol were increased, while levels of proinflammatory cytokines (TNFa, IL1b, and IL6) were markedly reduced in the exercised mice. The exercised mice developed lower levels of lipid content and inflammation in atherosclerotic plaques. Additionally, lesions in the exercised mice had lower levels of oxidative and ER stress markers. BMDM isolated from the exercised mice showed a marked reduction in proinflammatory cytokine gene expression and migratory activity and a disrupted motility phenotype. More importantly, bone marrow from exercised mice transplanted into sedentary mice led to reduced atherosclerosis in the recipient sedentary mice, thus suggesting that epigenetic mechanisms are associated with exercise. Collectively, the presented data indicate that exercise training prevents atherosclerosis by inhibiting bone marrow-derived macrophage recruitment and activation.
Español: Un evento temprano en la aterogénesis es el reclutamiento e infiltración de monocitos circulantes y la activación de macrófagos en el espacio subendotelial. Posteriormente, la aterosclerosis progresa como una enfermedad inflamatoria no resuelta, particularmente en condiciones hipercolesterolémicas. Aunque el entrenamiento con ejercicio físico ha sido una estrategia ampliamente aceptada para inhibir la aterosclerosis, su impacto sobre la inflamación de la pared arterial y el fenotipo y función de los macrófagos aún no se ha evaluado directamente. Por lo tanto, el objetivo de este estudio fue investigar los efectos del entrenamiento con ejercicios aeróbicos sobre el estado inflamatorio de las lesiones ateroscleróticas centrándose en los macrófagos. Se sometió a ratones machos hipercolesterolémicos con deficiencia del receptor LDL a un entrenamiento en cinta rodante durante 8 semanas y se les alimentó con una dieta rica en grasas. Los análisis incluyeron niveles plasmáticos de lipoproteínas y citocinas; tinción de la raíz aórtica para lípidos (rojo aceite O); macrófagos (CD68, MCP1 e IL1β); marcadores de estrés oxidativo (nitrotirosina y DHE) y del retículo endoplásmico (GADD). Se analizó la actividad migratoria, el fenotipo de motilidad (Rac1 y actina F) y la expresión génica relacionada con la inflamación en macrófagos primarios derivados de la médula ósea (BMDM). Los niveles plasmáticos de colesterol HDL aumentaron, mientras que los niveles de citoquinas proinflamatorias (TNFa, IL1b e IL6) se redujeron notablemente en los ratones ejercitados. Los ratones ejercitados desarrollaron niveles más bajos de contenido de lípidos e inflamación en las placas ateroscleróticas. Además, las lesiones en los ratones ejercitados tenían niveles más bajos de marcadores de estrés oxidativo y del RE. La BMDM aislada de ratones ejercitados mostró una marcada reducción en la expresión del gen de citoquinas proinflamatorias y en la actividad migratoria y un fenotipo de motilidad alterado. Más importante aún, la médula ósea de ratones ejercitados trasplantada a ratones sedentarios condujo a una reducción de la aterosclerosis en los ratones sedentarios receptores, lo que sugiere que los mecanismos epigenéticos están asociados con el ejercicio. En conjunto, los datos presentados indican que el entrenamiento físico previene la aterosclerosis al inhibir el reclutamiento y la activación de los macrófagos derivados de la médula ósea. |
| Date | |
| Source | https://figshare.com/articles/figure/Image_1_The_Anti-atherogenic_Role_of_Exercise_Is_Associated_With_the_Attenuation_of_Bone_Marrow-Derived_Macrophage_Activation_and_Migration_in_Hypercholesterolemic_Mice_TIFF/13272398/1 |
| Author | Figshare |
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