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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2174.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Severe Periodontitis Enhances Macrophage Activation via Increased Serum Lipopolysaccharide

Pirkko J. Pussinen; Tiina Vilkuna-Rautiainen; Georg Alfthan; Timo Palosuo; Matti Jauhiainen; Jouko Sundvall; Marja Vesanen; Kimmo Mattila; Sirkka Asikainen

From the Institute of Dentistry (P.J.P., T.V.-R., M.V., K.M.), University of Helsinki, and the Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland; the Department of Health and Functional Ability (G.A., T.P., J.S.) and the Department of Molecular Medicine (M.J.), National Public Health Institute, Helsinki, Finland; and the Department of Oral Microbiology (S.A.), Umeå University, Umeå, Sweden.

Correspondence to Pirkko Pussinen, Institute of Dentistry, University of Helsinki, PO Box 63 (Haartmaninkatu 8), FIN-00014, Helsinki University, Finland. E-mail pirkko.pussinen{at}helsinki.fi

Objective— In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation.

Methods and Results— LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30±0.19 versus 1.48±0.28 mmol/L; P=0.002) and HDL/LDL ratio (0.31±0.01 versus 0.34±0.10; P=0.048), but lower serum LPS concentration (1.70±0.49 versus 0.98±0.50 ng/mL; P=0.004) and autoantibodies to ß₂-glycoprotein I (0.11±0.06 versus 0.09±0.04 ELISA units; P=0.022) after treatment.

Conclusions— Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.

The effect of periodontal treatment on proatherogenic properties of LDL and, thus, macrophage activation was investigated. LDL was isolated and LDL-associated proatherogenic parameters were determined from 30 systemically healthy patients with periodontitis. Our results suggest that the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS.

Key Words: inflammation • infection • lipoprotein metabolism • serum lipopolysaccharide

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