Oral Infection With a Periodontal Pathogen Accelerates Early Atherosclerosis in Apolipoprotein E–Null Mice

Abstract

Objective—Because recent epidemiologic evidence suggests that periodontal infections may increase the risk of atherosclerosis and related events in humans, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on atherogenesis in hypercholesterolemic apolipoprotein E–null mice. Methods and Results—In the absence of alterations in distinct risk factors,P gingivalis infection exacerbated the early stages of atherogenesis in this model. Infected animals displayed evidence of local periodontal infection, as the severity of alveolar bone loss, the hallmark of periodontitis, was increased. Generalized activation of host inflammatory responses was evident in infected mice, as demonstrated by serum IgG response to P gingivalis and elevated levels of interleukin-6.P gingivalis DNA was localized in the aortic tissue from a limited number of infected mice but not in any noninfected controls. Infected mice displayed enhanced vascular activation, as suggested by increased aortic expression of vascular cell adhesion molecule-1 and tissue factor. Conclusions—Oral infection with P gingivalis accelerates early atherosclerosis. Thus, uncovering the underlying mechanisms is critical for the design of preventive and therapeutic strategies targeting atherosclerotic vascular disease and its sequelae.