Lipoprotein profile in periodontitis and its role in cardiovascular disease

Modified LDL has been suggested to initiate the formation of atheromas by inducing an inflammatory reaction involving influx of monocytes and T-lymphocytes into the vessel wall in response to the endothelial perturbation. We have previously shown that incubation of human whole blood with the periodontal pathogen Porphyromonas gingivalis causes leukocyte/platelet aggregate formation and ROS production and markedly modifies LDL through a gingipain R-mediated cleavage of apoB-100 and increased expression of apoM (Bengtsson et al., 2008; Borgesson et al., 2011) Consequently, our findings together with others suggest that P. gingivalis during translocation in circulating blood modifies LDL to an atherogenic form which supports a role of periodontal disease in the development of atherosclerosis. Preliminary studies of the lipoproteome in plasma of patients with periodontitis, using 2D gel electrophoresis and MALDI TOF mass spectrometry, show significant changes in the expression of several apo-proteins in LDL, compared to healthy controls, for example, increased expression of apoE, apoM, apoC and SAA, and decreased expression of apoA1- effects that are associated with an increased uptake of cholesterol and triglycerides into vessel walls. Antibodies against P. gingivalis and P. gingivalis-modified-LDL have been produced by our group in vitro by lymphocyte cultures and memory cells and then immobilized in a biosensor Surface Plasmon Resonance system. Most interestingly, we have found that these antibodies recognize modified LDL and P. gingivalis, respectively, in patients with periodontitis with high sensitivity and specificity.

The intentions with this project are to: i) study the expression of lipoproteins and other inflammatory markers in saliva and plasma of patients with periodontitis and/or cardiovascular disease by using proteomic analysis ii)analyze the presence of P. gingivalis and P. gingivalis-modified LDL in saliva, plasma and atherosclerotic plaques in patients with coronary artery disease iii) evaluate the effects of active and passive immunization with P. gingivalis or P. gingivalis-modifed LDL in atherogenic mouse models.

This project has been supported by the Swedish Heart-Lung Foundation and the Knowledge Foundation.

References

- Bengtsson, T., Karlsson, H., Gunnarsson, P., Skoglund, C., Elison, C., Leanderson, P., and Lindahl, M. (2008) The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation. J Intern Med. 263:558-571.

- Börgeson, E., Lönn, J., Bergström, I., Brodin, V.P., Nayeri, F., Särndahl, E., and Bengtsson, T. (2011) Lipoxin A4 inhibits Porphyromonas gingivalis-induced aggregation and ROS-production – role of Rho GTPase activity and CD11b expression. Infection&Immunity 79:1489-1497.

- Khalaf, H., Lönn, J., Bengtsson, T. (2014) Cytokines and chemokines are differentially expressed in patients with periodontitis: possible role for TGF-beta as a marker for disease progression. Cytokine, 67:29-35.