title: Effect of aerobic exercise on miRNA-TLR4 signaling in atherosclerosis.
abstract: Toll-like receptor 4 (TLR4)-tumor necrosis factor receptor 6 (TRAF6) signaling is activated in atherosclerosis (AS), inducing inflammatory mediators. Because miR-146a, a TLR4 microRNA (miRNA), can regulate TLR4 signaling during inflammatory responses, this study investigated the effects of aerobic exercise on TLR4-targeted miRNAs in AS. Apolipoprotein E-null mice fed a high-fat diet for 12 weeks were separated into 3 groups: (i) no treatment (AS), (ii) statin treatment (AD), or (iii) aerobic exercise (AE). Plaques and foam cells were observed in the untreated control and statin groups, respectively, but not in the AE group. Reduced angiotensin II (Ang II) and endothelin 1 (ET1) levels were observed in the AE group. Both treatment groups significantly altered the expression of inflammatory cytokine expression and reduced vascular TLR4 levels. Increased miR-146a and miR-126 and reduced miR-155 levels were observed in both treatment groups (all, P<0.001). miR-146a interacted with the 3' untranslated region of the TRAF6 gene, reducing its expression. Thus, aerobic exercise and statins may induce miR-146a expression, thereby reducing vascular TRAF and TLR4 signaling and vascular inflammatory injury in AS. Further analysis of this pathway may provide insight into the protective effects of aerobic exercise on vascular disease as well as new therapeutic targets.
authors.affiliation: Anesthesiology, Fujian Provincial Clinical Medical College, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: X-D
authors.initials: XD
authors.lastname: Wu
authors.affiliation: Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: K
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Rehabilitation, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
authors.forename: W-L
authors.initials: WL
authors.lastname: Liu
authors.affiliation: Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Y-G
authors.initials: YG
authors.lastname: Gao
authors.affiliation: Anesthesiology, Fujian Provincial Clinical Medical College, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: C-S
authors.initials: CS
authors.lastname: Gong
authors.affiliation: Physical Education, Institute of Human Movement Sciences Research, Hunan Normal University, Changsha, China.
authors.forename: C-X
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: Anesthesiology, Fujian Provincial Clinical Medical College, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D004815:Epidermal Growth Factor / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000097:blood*; D016328:NF-kappa B / Q000097:blood; D010805:Physical Conditioning, Animal; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000097:blood*
chemical_list: D019332:Endothelin-1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D035683:MicroRNAs; D016328:NF-kappa B; C495345:TLR4 protein, human; D048029:TNF Receptor-Associated Factor 6; D051197:Toll-Like Receptor 4; D000804:Angiotensin II; D004815:Epidermal Growth Factor