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Modified Lipoproteins in Periodontitis: A Link to Cardiovascular Disease?


Modified Lipoproteins in Periodontitis: A Link to Cardiovascular Disease?

Stefan Ljunggren et al. Biosci Rep.


There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of α-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. α-1 antitrypsin and α-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).

Keywords: lipoproteins; nLC-MS/MS; periodontal microbiota; periodontitis; two-dimensional gel electrophoresis.

Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.


Figure 1
Figure 1. Frequency distribution and amount of bacterial species in the subgingival plaque of ten patients with severe periodontitis investigated using DNA–DNA hybridisation technique
The presence of 11 bacterial species associated with subgingival bacterial flora were detected. The number of bacteria found is expressed in a scoring system (0–5), where score 0–1 corresponds to 0–105, score 2–3 corresponds to 105–106 and 4–5 corresponds to ≥106 bacteria. The IF indicate the number of patients in which the species were found.
Figure 2
Figure 2. 2-DE pattern of LDL/VLDL and HDL proteins from controls and patients
A total of 400 and 300 µg of proteins were loaded on HDL and LDL/VLDL gels, respectively. Proteins were visualised by SYPRO Ruby protein staining for HDL and silver staining for LDL/VLDL.
Figure 3
Figure 3. The carbonylation pattern was evaluated by Oxyblot of two 2D gels of LDL/VLDL isolated from one patient with periodontitis and one control
Figure 4
Figure 4. Multivariate modelling of all variables
(A) Score scatter plot showing the separation of patients and controls along the predictive x-axis. (B) Loading plot of variables with a VIP-value >1.5. Variables to the left are decreased while variables to the right are increased in patients compared with controls.

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