Porphyromonas gingivalis promotes low-density lipoprotein oxidation and atherosclerosis

Objectives Recent studies have reported that periodontal disease increases the risk of atherosclerosis. We previously reported that Porphyromonas gingivalis (Pg) accelerated atherosclerotic plaque formation in hyperlipidemic apoE-/- mice by initiating inflammation. Because the oxidative modification of lipoprotein plays a major role in atherosclerosis, we characterized the reactive oxygen species (ROS) produced by Pg and its ability to oxidize low-density lipoprotein (LDL). Methods Atherosclerotic plaque formation in the aortic sinuses of Apoe^shl mice injected intravenously with Pg 381 was assessed by Oil Red O staining. Anti-mouse antibodies to HOCl-oxidized LDL and 4-HNE, PLA2, MPO, and CD36 were used for immunohistochemistry. Intracellular ROS detection was performed using 2′,7′-dichlorodihydrofluorescein diacetate. Quantitative reverse transcription polymerase chain reaction was performed using primers specific for TLR-2, TLR-4, TLR-9, NOD-1, LOX-1, NOX-2, NOX-4, p22phox, and p47phox. Results Pg challenge significantly induced ox-LDL and 4-HNE-, PLA2-, MPO-, and CD36-positive areas in proximal aortic lesions. TLR-2, TLR-4, NOD-1, LOX-1, and NADPH oxidase subunit-specific mRNA levels in the aorta were significantly increased. Furthermore, Pg significantly induced ROS production in monocytes. Conclusions These results suggest that Pg promotes LDL oxidation and contributes to atheroma development.