Periodontal pathogen accelerates lipid peroxidation and atherosclerosis.
Recent studies have shown an association between periodontal disease and cardiovascular disease. We previously reported that intravenous challenge with Aggregatibacter actinomycetemcomitans (Aa) accelerated atherosclerosis in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether live cells were required for atherosclerosis induction or whether lipopolysaccharide (LPS) alone was sufficient to increase atherosclerotic damage. Mice were injected intravenously with live Aa HK1651, heat-killed (H.K.) Aa, or Aa LPS 3 times a week for 3 weeks and were sacrificed at 15 weeks of age. The areas of the aortic sinus that were covered with atherosclerotic plaques were significantly larger in mice treated with live Aa, H.K. Aa, or Aa LPS compared with vehicle-challenged mice. The order of the extent of atherosclerosis was live Aa > H.K. Aa > Aa LPS > sham. Toll and nucleotide oligomerization domain (NOD)-like receptor mRNA expression significantly increased in the live Aa, H.K. Aa, and Aa LPS treatment groups. Aa challenge markedly promoted the oxidation of LDL through oxidative stress involving NADPH oxidase- and myeloperoxidase-derived reactive oxygen species. These results suggested that Aa promoted innate immune signaling and low-density lipoprotein (LDL) oxidation and may facilitate atheroma development.
Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-nishi, Matsudo, Chiba 271-8587, Japan.
R
R
Jia
T
T
Kurita-Ochiai
S
S
Oguchi
M
M
Yamamoto
D016976:Aggregatibacter actinomycetemcomitans / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000382:microbiology*; D051242:Caveolin 1 / Q000097:blood; D005260:Female; D006358:Hot Temperature; D007113:Immunity, Innate / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D019255:NADPH Oxidases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D053472:Nod Signaling Adaptor Proteins; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000097:blood; D051193:Toll-Like Receptors / Q000096:biosynthesis
D051242:Caveolin 1; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D053472:Nod Signaling Adaptor Proteins; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019255:NADPH Oxidases