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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The Anti-atherogenic Role of Exercise Is Associated With the Attenuation of Bone Marrow-Derived Macrophage Activation and Migration in Hypercholesterolemic Mice

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Author(s):
Rentz, Thiago [1] ; Wanschel, Amarylis C. B. A. [1] ; de Carvalho Moi, Leonardo [1] ; Lorza-Gil, Estela [1] ; de Souza, Jane C. [1] ; dos Santos, Renata R. [2] ; Oliveira, Helena C. F. [1]
Total Authors: 7
Affiliation:
[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas - Brazil
[2] Univ Estadual Campinas, Med Sch Hosp, Div Radiotherapy, Fac Med Sci, Campinas - Brazil
Total Affiliations: 2
Document type: Journal article
Source: FRONTIERS IN PHYSIOLOGY; v. 11, NOV 23 2020.
Web of Science Citations: 0
Abstract

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 IL1 beta); 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. (AU)

FAPESP's process: 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases
Grantee:Aníbal Eugênio Vercesi
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
Grantee:Licio Augusto Velloso
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC