Aggregatibacter actinomycetemcomitans induces MMP-9 expression and proatherogenic lipoprotein profile in apoE-deficient mice

Periodontitis increases the atherosclerosis risk, but information on the role of periodontal pathogens in atherogenesis is limited. In the present study we have investigated, whether the major periodontal pathogen, Aggregatibacter (Actinobacillus) actinomycetemcomitans, induces development of atherosclerosis in apolipoprotein E-deficient mice. The mice received 4, 6, or 8 weekly i.v. injections of live pathogen (10(7) CFU/50 mu l/mouse) or saline as control, and were killed 1 week after the last injection. The atherosclerotic lesion formation was examined from whole aortas and aortic sinus cryosections after lipid staining. Neither the lesion area in the aortas or en face analyses, nor their immunoreactivity to the macrophage-marker CD68 differed significantly between the infected and the control mice. However, the pathogen administration increased serum C-reactive protein (CRP) concentrations, and induced proatherogenic lipoprotein profiles with smaller particle sizes in very-low density (VLDL), low density (LDL), and high density (HDL) lipoprotein fractions. It also caused elevated matrix metalloproteinase-9 expression in the aortas and increased serum gelatinase level. Lipopolysaccharide deriving from the pathogen was associated with proatherogenic lipoprotein fractions: VLDL and especially LDL. The results indicate that A. actinomycetemcomitans contributes to disturbed lipoprotein profiles, inflammatory reaction, and matrix remodelling which are known to promote the development of atherosclerosis. (C) 2007 Elsevier Ltd. All rights reserved.