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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 (nϭ36) 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 10 9 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 10 6 to 10 7 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 gingivalischallenged 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. Key Words: coronary and aortic atherosclerosis Ⅲ Porphyromonas gingivalis Ⅲ periodontitis Ⅲ pig model Ⅲ bacteremia P eriodontitis has been associated with cardiovascular disease in many, but not all, epidemiological studies. 1-15 Mild forms of periodontal disease affect 75% of the population, and more severe forms affect 20% to 30% of adults in the United States. 8 The mechanism by which periodontitis could contribute to cardiovascular disease is unknown but likely relates to the associated intense local and systemic inflammation and the virulence properties of the causative organisms. 16 -21 Porphyromonas gingivalis has been strongly associated with adult periodontitis. This bacteria is a Gramnegative, nonmotile, obligate anaerobe that can invade and infect epithelium, endothelium, and vascular smooth muscle cells 22-29 and appears to alter endothelial function. 30 The capacity for invasion is in part mediated by fimbriae, 31,32 and the virulence of P gingivalis may vary among individual strains. 33 Recurrent bacteremias with P gingivalis and a mixture of other oral bacteria can occur in periodontitis patients during simple mastication. 34 -36 P gingivalis has been detected by immunostaining and polymerase chain reaction (PCR) in some human carotid and coronary atheromas. 27,37 In addition, P gingivalis produces arginine-specific cysteine proteases, called gingipain Rs, that can activate both the cellular and humoral coagulation systems. These gingipain Rs activate protease-activated receptors 1 and 4 (PAR-1 and PAR-4) on platelets to a degree sufficient to support ex vivo aggregation. 38 -42 Moreover, gingipain Rs can activate coagulation factors I...

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