Abstract
Recent epidemiological studies have shown that there is an association between periodontal disease and cardiovascular disease. We assessed the involvement of the periodontal pathogen Aggregatibacter actinomycetemcomitans in the development of atherosclerosis in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoeshl) mice. The mice were treated intravenously with A. actinomycetemcomitans HK1651 or vehicle three times a week for 3 weeks and killed at 15 weeks of age. Histomorphometric analysis of atheromatous lesions, en face analysis over the aortic tree, TUNEL staining for apoptotic cells, and gene expression in the aorta were examined. The areas of the aortic sinus that were covered with atherosclerotic plaque were larger in Apoeshl mice challenged with A. actinomycetemcomitans compared to controls. The A. actinomycetemcomitans challenge induced CD44, caspase-3 and caspase-7 expressions, and TUNEL-positive response for apoptosis in proximal aortic lesions in Apoeshl mice. An in vitro study using human umbilical vein endothelial cells indicated that A. actinomycetemcomitans lipopolysaccharide induced caspase-dependent apoptosis. These results suggest that systemic infection with A. actinomycetemcomitans accelerates atherosclerosis in Apoeshl mice through endothelial cell dysfunction.
