The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 in LDL in whole blood

Objective: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims to investigate the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system by using a proteomic approach and analyze the effects of P. gingivalis-modifed LDL on cell proliferation. Methods: The cellular effects of P. gingivalis in human whole blood were assessed using lumiaggregometry analyzing reactive oxygen species (ROS) production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analyzing the formation of protein carbonyls. The effects of P. gingivalis-modifed LDL on fibroblast proliferation were studied using the MTS-assay. Results: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROSproduction, indicating platelet and leukocyte activation. LDL prepared from the bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB100 N-terminal fragments. P. gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis. Conclusions: The ability of P. gingivalis to change the protein expression and the proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.