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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The periodontal pathogen Porphyromonas gingivalis is implicated in certain systemic diseases including atherosclerosis and aspiration pneumonia. This organism induces innate responses predominantly through TLR2, which also mediates its ability to induce experimental periodontitis and accelerate atherosclerosis. Using a validated mouse model of intratracheal challenge, we investigated the role of TLR2 in the control of P. gingivalis acute pulmonary infection. TLR2-deficient mice elicited reduced proinflammatory or antimicrobial responses (KC, MIP-1alpha, TNF-alpha, IL-6, IL-12p70, and NO) in the lung and exhibited impaired clearance of P. gingivalis compared with normal controls. However, the influx of polymorphonuclear leukocytes into the lung and the numbers of resident alveolar macrophages (AM) were comparable between the two groups. TLR2 signaling was important for in vitro killing of P. gingivalis by polymorphonuclear leukocytes or AM and, moreover, the AM bactericidal activity required NO production. Strikingly, AM were more potent than peritoneal or splenic macrophages in P. gingivalis killing, attributed to diminished AM expression of complement receptor-3 (CR3), which is exploited by P. gingivalis to promote its survival. The selective expression of CR3 by tissue macrophages and the requirement of TLR2 inside-out signaling for CR3 exploitation by P. gingivalis suggest that the role of TLR2 in host protection may be contextual. Thus, although TLR2 may mediate destructive effects, as seen in models of experimental periodontitis and atherosclerosis, we have now shown that the same receptor confers protection against P. gingivalis in acute lung infection.
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PMID:Importance of TLR2 in early innate immune response to acute pulmonary infection with Porphyromonas gingivalis in mice. 1876 71

Available evidence does allow an interpretation of periodontitis as being a risk factor for atherosclerosis and coronary heart disease. There is now a convincing body of evidence that mechanism of atherosclerosis has a major inflammatory component and it is much more than the simple accumulation of lipids on the vascular walls. Studies have shown that certain other mild bacterial infections consist a major risk factor for stroke in young and middle aged patients. Several possible mechanisms could explain the observed association between infection and infraction. The evidence supports the premise that periodontitis leads to systemic exposure to oral bacteria and that the resulting production of inflammatory mediators is capable of initiating or supporting mechanisms associated to development of atherosclerosis and coronary heart disease. Studies in patients with pathologic concentrations of anti-cardiolipin and anti-phosphorylcholine antibodies demonstrated increased pocket depth and attachment loss, compared to patients with normal levels of the above antibodies. These antibodies could be associated to increased risk for stroke and atherosclerosis in patients with periodontitis. As we become more familiar to the association between periodontitis and cardiovascular disease it is likely that in the future periodontal disease may be added to the list of the factors which are used to assess patients' risk profile for coronary heart disease and stroke.
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PMID:Periodontitis as a risk factor for cardiovascular disease: the role of anti-phosphorylcholine and anti-cardiolipin antibodies. 1892 69

The microbial community present in the human mouth is engaged in a complex network of diverse metabolic activities. In addition to serving as energy and building-block sources, metabolites are key players in interspecies and host-pathogen interactions. Metabolites are also implicated in triggering the local inflammatory response, which can affect systemic conditions such as atherosclerosis, obesity, and diabetes. While the genome of several oral pathogens has been sequenced, quantitative understanding of the metabolic functions of any oral pathogen at the system level has not been explored yet. Here we pursue the computational construction and analysis of the genome-scale metabolic network of Porphyromonas gingivalis, a gram-negative anaerobe that is endemic in the human population and largely responsible for adult periodontitis. Integrating information from the genome, online databases, and literature screening, we built a stoichiometric model that encompasses 679 metabolic reactions. By using flux balance approaches and automated network visualization, we analyze the growth capacity under amino-acid-rich medium and provide evidence that amino acid preference and cytotoxic by-product secretion rates are suitably reproduced by the model. To provide further insight into the basic metabolic functions of P. gingivalis and suggest potential drug targets, we study systematically how the network responds to any reaction knockout. We focus specifically on the lipopolysaccharide biosynthesis pathway and identify eight putative targets, one of which has been recently verified experimentally. The current model, which is amenable to further experimental testing and refinements, could prove useful in evaluating the oral microbiome dynamics and in the development of novel biomedical applications.
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PMID:Metabolic network model of a human oral pathogen. 1893 Nov 37

Periodontitis is a bacterium-induced chronic inflammation that destroys tissues that attach teeth to jaw bone. Pathologically excessive matrix metalloproteinase 8 (MMP-8) is among the key players in periodontal destruction by initiating type I collagen degradation. We studied MMP-8 in Porphyromonas gingivalis-induced periodontitis by using MMP-8-deficient (MMP8(-/-)) and wild-type (WT) mice. Alveolar bone loss, inflammatory mediator expression, serum immunoglobulin, and lipoprotein responses were investigated to clarify the role of MMP-8 in periodontitis and systemic inflammatory responses. P. gingivalis infection induced accelerated site-specific alveolar bone loss in both MMP8(-/-) and WT mice relative to uninfected mice. The most extensive bone degradation took place in the P. gingivalis-infected MMP8(-/-) group. Surprisingly, MMP-8 significantly attenuated (P < 0.05) P. gingivalis-induced site-specific alveolar bone loss. Increased alveolar bone loss in P. gingivalis-infected MMP8(-/-) and WT mice was associated with increase in gingival neutrophil elastase production. Serum lipoprotein analysis demonstrated changes in the distribution of high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL) particles; unlike the WT mice, the MMP8(-/-) mice underwent a shift toward a smaller HDL/VLDL particle sizes. P. gingivalis infection increased the HDL/VLDL particle size in the MMP8(-/-) mice, which is an indicator of lipoprotein responses during systemic inflammation. Serum total lipopolysaccharide activity and the immunoglobulin G-class antibody level in response to P. gingivalis were significantly elevated in both infected mice groups. Thus, MMP-8 appears to act in a protective manner inhibiting the development of bacterium-induced periodontal tissue destruction, possibly through the processing anti-inflammatory cytokines and chemokines. Bacterium-induced periodontitis, especially in MMP8(-/-) mice, is associated with systemic inflammatory and lipoprotein changes that are likely involved in early atherosclerosis.
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PMID:Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis. 1902

Chlamydia pneumoniae is an obligate intracellular Gram-negative bacterium with a unique biphasic developmental cycle that can cause persistent infections. In humans, Chlamydia causes airway infection and has been implicated in chronic inflammatory diseases, such as asthma and atherosclerosis. In addition, recent studies demonstrated that patients with severe periodontitis can harbor C. pneumoniae, which can increase the risk for a host inflammatory response with weighty clinical sequelae. Previous studies have established that periodontal pathogenic bacteria (i.e. Gram-negative bacteria) can induce the synthesis and release of cytokines and other inflammatory mediators in human gingival fibroblasts. HGF are resident cells of the periodontium that respond to receptor stimulation by producing a variety of substances including cytokines and growth factors. Our results demonstrate that after 48 hr of incubation with viable C. pneumoniae HGF showed a proliferative response, as seen by both colorimetric MTT assay and direct cell count (30% and 35%, respectively). In addition, HGF incubated with viable or UV light-inactivated C. pneumoniae organisms showed an increase in the levels of IL-6 and IL-10, but not IL-4; on the contrary, HGF infected with heat-killed bacteria did not show a significant production of any of the cytokines considered. In conclusion, the present study suggests that C. pneumoniae may modulate the expression of IL-6 and IL-10 by human gingival fibroblasts. Further studies are warranted to clarify the molecular mechanisms of C. pneumoniae in the regulation of cytokine expression by host cells and to elaborate the relevant clinical implications.
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PMID:Chlamydia pneumoniae induces interleukin-6 and interleukin-10 in human gingival fibroblasts. 1903 53

Periodontal disease is associated with cardiovascular disease and is thought to accelerate systemic atherosclerosis. Here we examined the relationship between periodontitis and cardiovascular disease mortality in outpatients on hemodialysis using a retrospective analysis of 168 adult patients in New York City and North Carolina. During 18 months of follow-up, cardiovascular disease and all-cause mortality were determined from a centralized dialysis registry. One hundred patients had mild or no periodontal disease but the remaining 68 had moderate-to-severe disease defined as 2 or more teeth with at least 6 mm of inter-proximal attachment loss. At baseline, the proportion of males was significantly lower in the moderate-to-severe group. Compared with mild or no periodontal disease, moderate-to-severe disease was significantly associated with death from cardiovascular causes. Adjustment for age, gender, center and dialysis vintage, smoking status, and history of diabetes mellitus or hypertension did not diminish the strength of this association. Our findings suggest a need for larger studies to confirm this connection, along with intervention trials to determine if treating periodontitis reduces cardiovascular disease mortality in dialysis patients.
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PMID:Periodontal disease adversely affects the survival of patients with end-stage renal disease. 1928 57

It has been proposed for several decades that infections may be responsible for the accelerated development of atherosclerosis. The initiation of the atherosclerotic plaque is ascribed to focal accumulation of lipids. This explains the importance of plasma lipids in the development of atherosclerosis. Recent reports point towards a possible association between periodontal disease and increased risk for cardiovascular disease. Thus, periodontitis and cardiovascular disease may share common risk factors, and association between periodontitis and coronary heart disease may be due to the elevated levels of plasma lipids. Epidemiological and clinical studies have also suggested that there is a relationship between periodontal disease and impaired lipid metabolism. In this review, we summarized the potential link mechanisms in the association between periodontal infection and serum lipids.
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PMID:The Bi-Directional Relationship between Periodontal Disease and Hyperlipidemia. 1921 26

This study investigated the effect of mechanical infection control for periodontitis and periodontal surgery on the prevalence of well-established risk factors for atherosclerosis, and plasma levels of cytokines, antibodies against heat shock proteins and markers of systemic inflammation. Sixty-eight patients between 39 and 73 years of age with severe periodontitis who had been referred to four specialist periodontology clinics in Sweden were investigated. A fasting venous blood sample was taken at baseline and additional samples were collected after 3 and 12 months. A total of 54 patients underwent periodontal treatment. The periodontal treatment was successful, as pathogenic gingival pockets decreased significantly. Plasma glucose, lipids and markers of systemic inflammation were not significantly altered after 3 months. One year after the initial treatment, HDL-C concentrations were significantly increased (Delta0.08mmol/L) whereas LDL-C concentrations decreased (Delta0.23mmol/L). Haptoglobin concentrations were also lower. Interleukin-18 and interferon-gamma levels were also lower after 12 months (60ng/L (-23%) and 11ng/L (-97%) respectively). Treatment had no effect on plasma levels of IgA, IgG1, IgG2 antibodies against heat shock proteins. In conclusion, this study indicates that standard treatment for periodontal disease induces systemic changes in several biochemical markers that reflect the risk for atherosclerosis.
Atherosclerosis 2009 Oct
PMID:Periodontal treatment influences risk markers for atherosclerosis in patients with severe periodontitis. 1941 Oct 77

Atherosclerosis is an important component of coronary heart disease (CHD), which is the leading cause of death worldwide, including in Japan. Because atherosclerotic processes are typified by chronic inflammatory responses, which are similar to those elicited by chronic infection, the role of infection in promoting or accelerating atherosclerosis has received considerable focus. Increasing evidence supports the notion that periodontitis is associated with increased risk of atherosclerosis through dysfunction of endothelial cells induced by either periodontopathic bacteria or their products, or inflammatory mediators derived from infected periodontal tissue. Here we review whether periodontitis represents a risk factor for CHD or atherosclerosis, particularly in a Japanese population.
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PMID:Periodontal disease and risk of atherosclerotic coronary heart disease. 1963 50

Periodontal disease is a chronic inflammatory disorder by the anaerobic bacteria invasion into periodontal tissues including gingival connective tissue, periodontal ligament, and alveolar bone. Periodontitis is classified into two types, gingivitis and periodontitis. Diabetic patients tend to suffer from periodontitis with severe alveolar bone loss caused by lowered immune reaction and delayed tissue recovering. Periodontal pathogens such as P. gingivalis lipopolysaccharide (P-LPS) and several cytokines (TNF-alpha, IL-1 and IL-6) stimulate osteoclast differentiation in gingival connective tissue. Then, alveolar bone resorption progresses and the resultant tooth loss falls oral functions. It is confirmed that the incidence of periodontitis is 2- to 3-fold higher in diabetic patients than in non-diabetic subjects. Recently, many researches demonstrated that periodontitis affected diabetic condition, in which periodontal pathogen like P-LPS and TNF-alpha possibly elevated insulin resistance by inhibiting glucose incorporation into smooth muscle cells. Clinical study revealed that serum C-reactive protein (CRP) value increased in periodontitis patients and that periodontal treatment improved the level of HbA(1C) in diabetic patients. These data indicate that periodontal pathogen influenced systemic conditions and these are partly improved by periodontal therapy. Also, periodontal pathogen possibly promotes atherosclerosis formation. Further investigation is necessary to clarify the relationship between diabetes and periodontal disease.
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PMID:[Relationhip between diabetes and periodontal disease]. 1972 Dec


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