title: Rosiglitazone impedes Porphyromonas gingivalis-accelerated atherosclerosis by downregulating the TLR/NF-κB signaling pathway in atherosclerotic mice.
abstract: Porphyromonas gingivalis,a predominant periodontal pathogen, is known to accelerate atherosclerosis in hyperlipidemic animals via aberrant inflammatory responses. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to exert anti-inflammatory effects in vitro. The purpose of the present study was to investigate the potential protective role of the PPARγ agonist rosiglitazone in pathogen accelerated atherosclerosis in an apolipoprotein E-deficient (ApoE-/-) mouse model. ApoE-/- mice were inoculated intravenously with live P. gingivalis (strain 33277) or the buffer vehicle and treated with rosiglitazone or saline over a 10-week period. Their atherosclerotic status in aortic artery was assessed through histomorphometric analysis, inflammatory agent and lipid profiles in blood was determined by ELISA, and levels of relevant cytokines and Toll-like receptors (TLRs) in aortic tissues were evaluated using immunohistochemistry and quantitative PCR. P. gingivalis inoculation was associated with increased atherosclerotic plaque formation in the aorta and higher levels of serum pro-inflammatory cytokines (tumor necrosis factor-α, monocyte chemotactic protein-1 and interleukin-1β), but the serum lipid profile was not affected by P. gingivalis infection. Levels of tumor necrosis factor-α, monocyte chemotactic protein-1 intercellular cell adhesion molecule-1 and TLRs were higher in the aortic tissues of mice exposed to P. gingivalis, and activation of nuclear factor-κB was also observed. In both P. gingivalis-treated and -untreated ApoE-/- mice, rosiglitazone treatment was associated with less atherosclerotic plaque formation; lower serum inflammatory cytokines, total cholesterol, and low density lipoprotein cholesterol; higher levels of PPARγ, lower amounts of TLR2/4 and downregulated nuclear factor-κB activity in aortic tissues. These findings suggest that rosiglitazone mitigates or prevents P. gingivalis-accelerated atherosclerosis by inhibiting the inflammatory response via downregulation of the TLR/ nuclear factor-κB signaling pathway.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Pan
authors.forename: Lang
authors.initials: L
authors.lastname: Lei
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.forename: Houxuan
authors.initials: H
authors.lastname: Li
authors.forename: Fuhua
authors.initials: F
authors.lastname: Yan
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D016866:Bacteroidaceae Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology*; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D008055:Lipids / Q000097:blood; D008297:Male; D018345:Mice, Knockout; D016328:NF-kappa B / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists; D016966:Porphyromonas gingivalis / Q000254:growth & development; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D051193:Toll-Like Receptors / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D008055:Lipids; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D051193:Toll-Like Receptors; D000077154:Rosiglitazone