INTRODUCTION:

Periodontitis is a major risk factor for cardio vascular diseases [1] , lung diseases[2] and liver diseases[3]. The rate of cardiovascular diseases increases with increase in periodontitis. Severe tooth loss (likely to be due to periodontal disease) may be a predictor of cerebrovascular disease-silent cerebral infarct [4]. In the past, there have been several studies suggesting that microbes may play a role in the development of atherosclerosis. Chronic Chlamydia pneumoniae infection and periodontitis have been found to be associated with coronary atherosclerosis [5-7]. Athero-sclerosis is a major burden of modern society and ischemic heart disease is the leading cause of death worldwide, according to the 2011 report by the World Health Organisation [8]. inflammation plays an important role in the pathogenesis of atherosclerosis, and low-grade chronic systemic inflammation has been shown to be linked to adverse cardiovascular outcomes [9].

Atherosclerosis :

T he amount of evidence correlating the association between specific bacteria and coronary diseases developing as a result of atherosclerosis has increased over the last two decades. These findings have brought a new aspect to the etiology of the disease. The original classical hypotheses about the development of atherosclerosis did not include inflammation as a primary factor of the pathogenesis. One of the hypotheses assumed that changes of endothelium as a consequence of mechanical damage with subsequent contamination by toxins, metal ions, and free radicals lead to the formation of atherosclerotic plates [10-12]. Atherosclerosis begins as inflammatory reaction against the endothelial cells and artery wall components. The inflammation site attracts T and B lymphocytes , and macrophages etc. Among the risk factors are circulating lipoproteins, genetic predisposition, hyper-tension, smoking, obesity, and diabetes. Epidemiological studies further indicate that infection by various types of bacteria, including periodontopathic ones (Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans) and the presence of products of these bacteria (LPS, heat shock protein (HSP)) in serum contributed to the development of atherosclerosis [13]

Periodontitis :

Periodontitis is a multifactorial diseases it is not only due to the pathogenic bacterial or the immune mechanism but may also occur due to the genetic predisposition . It results in tooth loss in most of the adults.The cause sof the onset and progress of period ontitishave been investigated for hundreds of years. The first records concerning the disease now called periodontitis date back to the ninth and tenth centuries A.D. with Arabian physicians already ascribing the disease to soft plaque on teeth. The assumption that dental plaque was one of the significant etiological factors was confirmed as recently as the 1960s [14,15]. During this time, the first articles appeared in which the authors demonstrated that patients’ blood serum had enhanced levels of antigens reacting with dental plaque bacteria [16].

The typical symptom of periodontitis is the infection to the periodontal pocket caused by the gram negative anaerobic bacteria. The bacteria involved in pathogenesis of the disease are Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleates, Tannerella forsythia, Treponema denticola, and others.

Periodontitis and Atherosclerotic Process:

T here are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: (a) activation of innate immunity, (b) bacteremia related to dental treatment, (c) direct involvement of mediators activated by dental plaque antigens in atheroma processes, (d) involvement of cytokines and heat shock proteins from dental plaque [17].

Activation of Innate Immunity:

The characteristics of individual's immune response to infectious agents greatly determine the severity of periodontal diseases [18]. The oral cavity is exposed to the activity of the bacteria resulting in the interaction with the innate immunity and anti microbial peptide production . These anti microbial peptides are in the form of phagocytic granules in the mammals. The important ones are the defensins and cathelicidins. These kills various microorganisms.

Defensins and histatin present in the phagocyte granules are produced by mucosal epithelium and by salivary glands. Cathelicidin is produced by phagocytes, the epithelium and salivary glands. It binds LPS, neutralizes endotoxin activity and acts chemotactically on neutrophils, monocytes, T lymphocytes, and mast cells and exhibits bactericidal activity. Its presence in large quantities in the junctional epithelium as a result of the migration of neutrophils is of great importance for the defence of the oral cavity [19]. Functional defects of neutrophils are a risk factor of the development of aggressive periodontitis [20, 21]. Both the gram positive and gram negative bacteria contain components that causes damage to the periodontal structures. T he cell walls of Gram-negative bacteria are formed of peptidoglycans, polysaccharides, proteins, lipids, lipopolysaccharides, and lipoproteins The walls of Gram-positive bacteria consist of peptidoglycan, teichoic acid, and polysaccharides[22] . Peptidoglycan activate the cells through binding to the Toll-like receptor-2; they are recognized by the complement as well as by specific receptors and they also participate in the activation of the complement system [23]

Bacteremia Related to Dental Treatment:

Dental infection affecting the periodontium can spread into the systemic circulation by dental treatment procedures or teeth brushing and can induce bacteremia. Patients with untreated adult periodontitis are at greater risk of bacteremia after periodontal probing than patients with chronic gingivitis [24]. The predominant microorganism of dental plaque Streptococcus sanguis is associated with endocarditis[25]. Higher incidence is seen in antibiotic prophylaxis and lower incidence in orthodontic banding and de banding[26,27]

Involve Ment of Mediators Activated by Dental Plaque Antigens in Atheroma Process:

T he presence of Porphyromonas gingivalis and Streptococcus sanguis in atherosclerotic plaques in samples of veins after surgical reconstruction of venous system was established [28] . In a recent review the results of 16 studies investigating the presence of oral bacteria in atheromatous plaque were compared, identifying Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis as the most frequently occurring bacteria[29]. The relationship between atherosclerosis and Porphyromonas gingivalis was confirmed experimentally using the model of Apo E-null mice. The development of periodontitis and atherosclerosis was induced by oral inoculation by Porphyromonas gingivalis. Over the course of 4 months, the mice exhibited lipid stripes in which the presence of Porphyromonas gingivalis was detected, and in mice with periodontitis, higher serum levels of IL-6 and VCAM-1 in aorta were detected [30].

Cytokines and Heat Shock Proteins:

After stimulation by bacteria and their components , periodontal tissues produces a number of inflammatory cytokines chemokines ,prostaglandins PGE2, and NO [31,32]. Peptidoglycans the components of bacterial cell wall contribute to the activation of immune system. The presence of circulating oral bacteria or bacterial components may stimulate blood cells to produce cytokines. IL-6 levels significantly increased eight hours after scaling, while IL-8decreased [33]. Higher levels of IL-6 were detected in the sera of patients with periodontitis compared to healthy controls [34].Heat shock proteins (HSPs) are known to be the most immunogenic antigens of bacteria. The extensive homology between human and bacterial HSPs may play a role in the activation of atherosclerotic changes. Decreased proliferative responses of peripheral blood cells to HSP in periodontitis patients compared to control patients were found [35]. Studies have reported a correlation between Porphyromonas gingivalis bacteria and increased levels of corresponding antibodies against HSP 60 in patients’ sera [36].

CONCLUSION:

Periodontitis and atherosclerosis are multifactorial diseases the onset is seen in the childhood but the symptoms are seen in the adulthood. Since periodontitis is a risk factor of atherosclerosis frequent examination of the patients with chronic periodontitis should be done .Patients with the initial stages of periodontal inflammation should be examined carefully. Timely treatment for both the diseases will diminish the serious changes.

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Received on 09.06.2016 Modified on 22.06.2016

Research J. Pharm. and Tech 2016; 9(11):2017-2019.

DOI: 10.5958/0974-360X.2016.00411.X