Periodontal pathogens invade gingiva and aortic adventitia and elicit inflammasome activation in αvβ6 integrin-deficient mice (original) (raw)
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PLoS ONE, 2014
Atherosclerotic vascular disease is a leading cause of myocardial infarction and cerebrovascular accident, and independent associations with periodontal disease (PD) are reported. PD is caused by polymicrobial infections and aggressive immune responses. Genomic DNA of Porphyromonas gingivalis, the best-studied bacterial pathogen associated with severe PD, is detected within atherosclerotic plaque. We examined causal relationships between chronic P. gingivalis oral infection, PD, and atherosclerosis in hyperlipidemic ApoE null mice. ApoE null mice (n = 24) were orally infected with P. gingivalis for 12 and 24 weeks. PD was assessed by standard clinical measurements while the aorta was examined for atherosclerotic lesions and inflammatory markers by array. Systemic inflammatory markers serum amyloid A, nitric oxide, and oxidized low-density lipoprotein were analyzed. P. gingivalis infection elicited specific antibodies and alveolar bone loss. Fluorescent in situ hybridization detected viable P. gingivalis within oral epithelium and aorta, and genomic DNA was detected within systemic organs. Aortic plaque area was significantly increased in P. gingivalis-infected mice at 24 weeks (P,0.01). Aortic RNA and protein arrays indicated a strong Th2 response. Chronic oral infection with P. gingivalis results in a specific immune response, significant increases in oral bone resorption, aortic inflammation, viable bacteria in oral epithelium and aorta, and plaque development.
PLoS ONE, 2013
Periodontal disease (PD) and atherosclerosis are both polymicrobial and multifactorial and although observational studies supported the association, the causative relationship between these two diseases is not yet established. Polymicrobial infection-induced periodontal disease is postulated to accelerate atherosclerotic plaque growth by enhancing atherosclerotic risk factors of orally infected Apolipoprotein E deficient (ApoE null) mice. At 16 weeks of infection, samples of blood, mandible, maxilla, aorta, heart, spleen, and liver were collected, analyzed for bacterial genomic DNA, immune response, inflammation, alveolar bone loss, serum inflammatory marker, atherosclerosis risk factors, and aortic atherosclerosis. PCR analysis of polymicrobial-infected (Porphyromonas gingivalis [P. gingivalis], Treponema denticola [T. denticola], and Tannerella forsythia [T. forsythia]) mice resulted in detection of bacterial genomic DNA in oral plaque samples indicating colonization of the oral cavity by all three species. Fluorescent in situ hybridization detected P. gingivalis and T. denticola within gingival tissues of infected mice and morphometric analysis showed an increase in palatal alveolar bone loss (p,0.0001) and intrabony defects suggesting development of periodontal disease in this model. Polymicrobial-infected mice also showed an increase in aortic plaque area (p,0.05) with macrophage accumulation, enhanced serum amyloid A, and increased serum cholesterol and triglycerides. A systemic infection was indicated by the detection of bacterial genomic DNA in the aorta and liver of infected mice and elevated levels of bacterial specific IgG antibodies (p,0.0001). This study was a unique effort to understand the effects of a polymicrobial infection with P. gingivalis, T. denticola and T. forsythia on periodontal disease and associated atherosclerosis in ApoE null mice.
High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis
Periodontal disease (PD) is generated by microorganisms. These microbes can enter the general circulation causing a bacteraemia. The result can be adverse systemic effects, which could promote conditions such as cardiovascular disease. Level A evidence supports that PD is independently associated with arterial disease. PD is a common chronic condition affecting the majority of Americans 30 years of age and older. Atherosclerosis remains the largest cause of death and disability. Studies indicate that the adverse cardiovascular effects from PD are due to a few putative or high-risk bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola or Fusobacterium nucleatum. There are three accepted essential elements in the pathogenesis of atherosclerosis: lipoprotein serum concentration, endothelial permeability and binding of lipoproteins in the arterial intima. There is scientific evidence that PD caused by the high-risk pathogens can influence the pathogenesis triad in an adverse manner. With this appreciation, it is reasonable to state PD, due to high-risk pathogens, is a contributory cause of atherosclerosis. Distinguishing this type of PD as causal provides a significant opportunity to reduce arterial disease. BACKGROUND
Role of Periodontal Infection, Inflammation and Immunity in Atherosclerosis
Current Problems in Cardiology, 2020
Background: Inflammation plays a major role in the development and progression of cardiovascular disease (CVD) morbidity and mortality. The well-established relationship between periodontal disease (PD) and CVD may be causal. Left untreated, PD can lead to high systemic inflammation, thus contributing to inflammatory CVD, such as atherosclerosis. Multiple mechanisms have been proposed to elucidate the causal relationship between PD and its contribution to CVD.
Biomedical Journal of Scientific and Technical Research, 2021
The role of periodontal disease in the etiology of cardiovascular disease has recently received considerable attention. Previous studies have shown conflicting results as to whether periodontitis is associated with increased risk of cardiovascular disease, however, numerous recent studies have demonstrated that patients with chronic destructive periodontitis show evidence of systemic inflammation which can link chronic periodontitis and cardiovascular disease. Moreover, periodontitis and cardiovascular disease, share the same risk factors such as smoking, male gender, aging and diabetes. The aim of the current study was to evaluate whether such an association exists and to explore the mechanistic link between local and systemic inflammation and the relative role of the host response. The current study adds to the strong evidence for an association between periodontitis and cardiovascular disease, however, does not prove causation. Further research is needed to clarify the strength of association between cardiovascular disease and periodontal disease.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2003
Objective— Because recent epidemiologic evidence suggests that periodontal infections may increase the risk of atherosclerosis and related events in humans, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on atherogenesis in hypercholesterolemic apolipoprotein E–null mice. Methods and Results— In the absence of alterations in distinct risk factors, P gingivalis infection exacerbated the early stages of atherogenesis in this model. Infected animals displayed evidence of local periodontal infection, as the severity of alveolar bone loss, the hallmark of periodontitis, was increased. Generalized activation of host inflammatory responses was evident in infected mice, as demonstrated by serum IgG response to P gingivalis and elevated levels of interleukin-6. P gingivalis DNA was localized in the aortic tissue from a limited number of infected mice but not in any noninfected controls. Infected mice displayed enhanced vascular activation, a...
Systemic Effects of Periodontal Diseases: Focus on Atherosclerosis
Periodontal Diseases - A Clinician's Guide, 2012
Periodontitis is a bacterially induced, localized, chronic inflammatory disease of periodontium that destroys connective tissues and bone supporting the teeth and may lead to tooth exfoliation and edentulism. Periodontitis is one of the most prevalent infectious diseases in humans. Mild forms affect 30% to 50% of adults and the severe generalized form affects 5% to 15% of the US adults (Periodontology, 2005). It is associated with specific bacterial groups, components of the dental biofilm, one of them (the "red complex") closely related to clinical measures of periodontal disease (Socransky et al., 1998). Periodontal pathogens normally inhabit the oral cavity as constituents of the dental biofilm. Since they are in intimate contact with the gingival epithelial tissues, they, however, can breach the gingival mucosal barrier at the ulcerative lesion and enter the circulation. Indeed, these organisms have been implicated in infections at distant sites, such as the central nervous system (Ewald et al., 2006), and measures of periodontitis (tooth loss) has been linked to subclinical atherosclerotic vascular disease (carotid artery plaque prevalence) (Desvarieux et al., 2003). Systemic dissemination can be a result of tissue invasion, or of dental procedures including personal oral hygiene, leading to bacteremia. Tissue invasion is very likely a key virulence factor for a bacterium since it provides a "privileged niche" (Falkow, 1997) with access to host nutritional and iron substrates and a shelter from the host humoral and cellular immune response. Intracellular localization also brings about bacterial persistence, critical property of a causative agent of a chronic disease. Atherosclerosis is a chronic inflammatory focal proliferative lesion of the arteries associated with conventional risk factors such as hypercholesterolemia, hypertension, diabetes and smoking, in addition to genetic factors (Libby and Theroux, 2005). However, the incidence of AS is not fully explained by these risk factors. It is now accepted that inflammation as a key integrative process playing a major role in the initiation and progression of atherosclerotic lesions, with the active participation of smooth muscle cells, leukocytes, growth factors and inflammatory mediators. A dynamic and progressive process, atherogenesis begins with endothelial dysfunction ("response to injury" model) that also interacts with the standard risk factors (Van Dyke and Kornman, 2008), (Libby et al., 2009). Novel diagnostic and treatment modalities targeting vascular inflammation are dependent on further investigations of the origins of the inflammation. The focus of this review is the
Cardiovascular disease, inflammation, and periodontal infection
Periodontology 2000, 2007
Inflammation plays a central and continuous role in the pathogenesis of atherosclerosis from its initiation to the development of clinical complications (Table 1) (58, 60). Normally, endothelial cells, which form the innermost surface of the artery wall, resist adhesion by circulating leukocytes. Several exposures or risk factors for atherosclerosis upset this homeostasis. Factors, such as a smoking, hypertension,
Invasion of human coronary artery cells by periodontal pathogens
Infection and immunity, 1999
There is an emerging paradigm shift from coronary heart disease having a purely hereditary and nutritional causation to possibly having an infectious etiology. Recent epidemiological studies have shown a correlation between periodontal disease and coronary heart disease. However, to date, there is minimal information as to the possible disease mechanisms of this association. It is our hypothesis that invasion of the coronary artery cells by oral bacteria may start and/or exacerbate the inflammatory response in atherosclerosis. Since a few periodontal pathogens have been reported to invade oral epithelial tissues, we tested the ability of three putative periodontal pathogens-Eikenella corrodens, Porphyromonas gingivalis, and Prevotella intermedia-to invade human coronary artery endothelial cells and coronary artery smooth muscle cells. In this study we demonstrate by an antibiotic protection assay and electron microscopy that specific species and strains invade coronary artery cells ...