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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1446.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Porphyromonas gingivalis Bacteremia Induces Coronary and Aortic Atherosclerosis in Normocholesterolemic and Hypercholesterolemic Pigs

Nadine Brodala; Elizabeth P. Merricks; Dwight A. Bellinger; Damrong Damrongsri; Steven Offenbacher; James Beck; Phoebus Madianos; Daniela Sotres; Yu-Ling Chang; Gary Koch; Timothy C. Nichols

From the School of Dentistry and Department of Periodontology (N.B., D.D., S.O., J.B., P.M.), the Department of Pathology and Laboratory Medicine (E.P.M., D.A.B., T.C.N.), and the Department of Biostatistics (D.S., Y.-L.C., G.K.), University of North Carolina at Chapel Hill and the Center of Oral and Systemic Diseases, Chapel Hill, NC.

Correspondence to Timothy C. Nichols, MD, Francis Owen Blood Research Laboratory, Department of Pathology and Laboratory Medicine, UNC School of Medicine, CB#3114, 125 University Lake Rd, Chapel Hill, NC 27516-3114. E-mail tnichols{at}med.unc.edu

Objectives— The aim of this study was to determine whether recurrent intravenous injections with Porphyromonas gingivalis (P gingivalis), mimicking periodontitis-associated bacteremia, promotes coronary artery and aortic atherosclerosis in pigs.

Methods and Results— Pigs (n=36) fed low- or high-fat chow were divided into P gingivalis–sensitized and P gingivalis–challenged groups or P gingivalis–sensitized controls and saline-treated controls. Pigs were sensitized with 10⁹ killed P gingivalis subcutaneously. Four weeks later all sensitized pigs in the group to be challenged started intravenous injections thrice weekly for 5 months with 10⁶ to 10⁷ colony forming units of P gingivalis while controls received saline. Anti–P gingivalis antibody, serum cholesterol, and complete blood counts were assayed monthly. Pigs were euthanized 2 weeks after the last injection, and coronary arteries and aortas were analyzed by histomorphometry and immunohistochemistry. Anti–P gingivalis antibody was increased by P gingivalis exposure. P gingivalis–challenged pigs developed a significantly greater amount of coronary and aortic atherosclerosis than controls in the normocholesterolemic group and nearly significant in the hypercholesterolemic group. P gingivalis was detected by polymerase chain reaction in arteries from most (94%, 16 of 17) P gingivalis–challenged pigs but not controls.

Conclusions— Recurrent P gingivalis bacteremia induces aortic and coronary lesions consistent with atherosclerosis in normocholesterolemic pigs and increases aortic and coronary atherosclerosis in hypercholesterolemic pigs.

To determine whether recurrent intravenous injections with Porphyromonas gingivalis promotes coronary artery and aortic atherosclerosis, pigs fed low- or high-fat chow were divided into P gingivalis–challenged or control groups. P gingivalis–challenged pigs developed significantly greater amount of atherosclerosis in the normocholesterolemic group and nearly significant in the hypercholesterolemic group.

Key Words: coronary and aortic atherosclerosis • Porphyromonas gingivalis • periodontitis • pig model • bacteremia

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