Periodontitis is associated with platelet activation

Abstract

There is an epidemiological association between periodontitis and cardiovascular disease (CVD). In periodontitis, low grade systemic inflammation and bacteremia occur regularly. Such events may contribute to platelet activation and subsequent pro-coagulant state. This study aimed to investigate platelet activation in periodontitis patients.

The study is composed of two parts. In the first part, plasma levels of soluble(s) P-selectin and sCD40 ligand were measured as general markers of platelet activation in periodontitis patients (n = 85) and in healthy controls (n = 35). In the second part, surface-exposed P-selectin and the ligand-binding conformation of the glycoprotein IIb–IIIa complex (binding of PAC-1 antibody) were determined on individual platelets in whole blood of periodontitis patients (n = 18) and controls (n = 16). Patients had significantly elevated plasma levels of sP-selectin (P < 0.001) and increased binding of PAC-1 on isolated platelets (P = 0.033). Platelet activation was more pronounced in the patients with more severe periodontal disease, showing a severity-dependence. The levels of sCD40 ligand and of platelet-bound P-selectin were not increased.

Periodontitis is associated with increased platelet activation. Since platelet activation contributes to a pro-coagulant state and constitutes a risk for atherothrombosis, platelet activation in periodontitis may partly explain the epidemiological association between periodontitis and CVD.

Introduction

Periodontitis is a chronic infectious disease of the supportive tissues of the teeth, which may lead to loss of teeth. It is one of the most common infections in humans, affecting in its most severe form, approximately 10% of the population [1]. Inflammation of periodontal tissues results in periodontal pocket formation and ulceration of the epithelial lining. In this way, periodontal pockets form ports of entry which may lead to transient bacteremias [2], [3]. Regularly occurring bacteremias in periodontitis patients underlie chronic production of pro-inflammatory mediators like interleukin (IL)-1β, IL-6, C-reactive protein and tumor-necrosis factor (TNF)-α [4], [5], [6].

One of the features of systemic inflammation is an increase in the number of platelets and platelet activation [7]. Also periodontitis has been associated with elevated numbers of platelets [8]. Furthermore, platelet numbers decrease after periodontal therapy [9]. Interestingly, strains of the recognized periodontal pathogen Porphyromonas gingivalis (P. gingivalis), but also other dental plaque bacteria, such as Streptococcus sanguis, induce platelet activation and aggregation in vitro and in animal studies [10], [11]. Activation of platelets leads to their release of pro-inflammatory mediators and exposure of pro-inflammatory receptors, resulting in platelet binding to leukocytes and endothelial cells [7]. These functions make platelets essential participants in both thrombotic and inflammatory reactions across the vasculature [12]. Platelet activation has been implicated in the development of atherosclerosis, atherothrombosis and subsequent coronary vascular and cerebrovascular diseases [13].

Epidemiological and intervention studies have associated periodontitis with atherosclerosis and cardiovascular diseases (CVD). The underlying mechanisms of this relationship are still obscure [14], [15]. Nevertheless endotoxemia and in particular, systemic exposure to P. gingivalis and the severity of periodontal disease seem be important risk factors for CVD in periodontitis patients [16], [17], [18], [19]. We hypothesize that platelet activation in periodontal patients may be an important link between periodontitis and CVD.

The aim of this study was to investigate whether periodontitis patients have a higher state of platelet activation compared to healthy controls.