Modified lipoproteins in periodontitis: a link to cardiovascular disease?

Stefan Ljunggren,Bijar Ghafouri,Julia Davies,Helen Karlsson,Johanna Lönn,Fariba Nayeri,Eleonor Palm,Torbjörn Bengtsson,Carin Starkhammar Johansson,Gunnel Svensäter

doi:10.1042/bsr20181665

Abstract

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).

Highlights

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally
The present study aims at identifying alterations of plasma lipoproteins in patients with periodontitis by analysing the protein expression and oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles
In one patient ‘the red complex’, P. gingivalis, T. forsythia and T. denticola, a group of bacteria that are associated with severe forms of periodontal disease, was found

Summary

Introduction

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. There is a strong association between atherosclerotic CVD and periodontal disease, where periodontitis is suggested to play a contributory role in CVD [1]. Both diseases are driven by chronic inflammatory responses. Periodontal diseases are the most common bacterially induced chronic inflammatory diseases in humans, affecting up to 90% of individuals worldwide [2] with over 7% of the global population suffering from severe periodontitis [3]. The host–pathogen interactions produce a destructive inflammatory response leading to ulceration of the gingival epithelium and eventually exposing the bacteria and their products to the bloodstream, thereby initiating a systemic inflammation [4]. An increasing body of evidence suggests that reactive oxygen species

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