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ABSTRACT: OBJECTIVE: Subantimicrobial-dose doxycycline (SDD) treatment has been reported to reduce the severity of chronic inflammation and to increase serum high-density lipoprotein cholesterol. In a double-blind, placebo-controlled clinical trial, we determined whether SDD affects the ability of serum to facilitate cholesterol removal from macrophages. METHODS: Forty-five postmenopausal osteopenic women with periodontitis were randomly assigned to take placebo (n = 26) or doxycycline hyclate (20 mg, n = 19) tablets twice daily for 2 years. Serum samples were collected at baseline, 1-, and 2-year appointments. The cholesterol efflux capacity of serum from cultured human macrophages (THP-1) was measured. RESULTS: SDD subjects demonstrated a significant increase in serum-mediated cholesterol efflux from macrophages at both time points compared to baseline (p < 0.04 for each). Mean cholesterol efflux levels over the first year of follow-up were 3.0 percentage points (unit change) higher among SDD subjects compared to placebo subjects (p = 0.010), while there was no significant difference in 2-year changes. There were no significant differences in the changes of apolipoprotein A-I, apolipoprotein A-II, or serum amyloid A levels between the groups. CONCLUSIONS: Our results suggest that SDD treatment may reduce the risk of cardiovascular disease in this patient group by increasing the cholesterol efflux capacity of serum.
Agents and Actions 05/2013; · 1.59 Impact Factor
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ABSTRACT: Background: Initiation and progression of periodontitis correlates with the increased quantities of periodontitis-associated bacteria in periodontal biofilms. In the present study, the aim was to measure Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis amounts in saliva and their antibody (Immunoglobulin-A and Immunoglobulin-G) levels in serum, and evaluate their diagnostic abilities, together or alone, in chronic periodontitis. Methods: Our study population comprised of 230 Finnish dentate adults: 84 with generalized chronic periodontitis (GCP), 65 with localized chronic periodontitis (LCP), and 81 control subjects without periodontitis. General and oral health information was obtained by questionnaires, interviews, and clinical and radiographic examinations. Salivary and serum samples were analyzed by quantitative single copy gene-based real-time polymerase chain reaction and multi-serotype enzyme-linked immunosorbent assays, respectively. Results: Pathogen carriers suffered mostly from GCP but seldom from LCP. A. actinomycetemcomitans and P. gingivalis quantities in saliva associated strongly with corresponding serum IgA and IgG values (p < 0.001) and with the severity of the disease (p < 0.001). P. gingivalis exhibited more straightforward associations between salivary bacterial burdens, corresponding antibody-formation, and the periodontitis severity than A. actinomycetemcomitans. The combination of information on age, sex, smoking habit and P. gingivalis results provided an area under curve (95% confidence interval, p) 0.817 (0.76-0.87, <0.001) for GCP. Conclusions: Combining saliva P. gingivalis quantity with the pathogen-specific host response may be used to diagnose periodontitis with high accuracy.
Journal of Periodontology 05/2013; · 2.60 Impact Factor
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ABSTRACT: Background: In this cross-sectional study we characterized the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography due to cardiologic problems, which may affect the oral microbiota. Methods: Pooled subgingival bacterial samples were collected from 477 dentate subjects during the oral examinations with periodontal probing depths (PD), bleeding on probing (BOP), and assessments of radiographic alveolar bone loss (ABL). The checkerboard DNA-DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes. Results: All bacterial combinations from the etiological bacterial group and each species from the red complex associated significantly (p < 0.001) with the grades of ABL. The prevalence of etiological bacterial group and the level of each species associated also strongly with the proportion of sites with PD 4-5 mm and ≥ 6 mm, BOP, and ABL except, A. actinomycetemcomitans. The level of gram-negative oral bacteria correlated significantly with that of gram-positive (r = 0.840, p < 0.001). In the multiple logistic regression analysis, the prevalence of the etiological bacterial group, the levels of gram-negative bacteria and Treponema denticola, and the prevalence of Porphyromonas gingivalis and T. denticola associated significantly with ABL, while other bacterial complexes or the level of gram-positive species did not. Conclusions: Although the levels of gram-negative and gram-positive species paralleled with periodontal parameters, only the species considered etiological were associated with the ABL.
Journal of Periodontology 03/2013; · 2.60 Impact Factor
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ABSTRACT: AIM: We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. MATERIALS AND METHODS: The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA-DNA hybridization assays. RESULTS: In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 10(5) A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00-3.35, p = 0.049), but its level or levels of other bacteria did not. CONCLUSIONS: The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.
Journal Of Clinical Periodontology 02/2013; · 3.00 Impact Factor
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ABSTRACT: OBJECTIVE: Periodontitis, a chronic oral infection caused mainly by gram-negative bacteria, induces endotoxemia and associates with the risk for atherosclerosis. We investigated the effect of periodontal treatment on proatherogenic properties of very low density lipoproteins (VLDL). METHODS: VLDL were isolated from 30 systemically healthy periodontitis patients before (pre-treatment) and 3months after treatment (post-treatment). The mass compositions were analyzed, and VLDL-induced changes in cellular cholesterol content and expression of selected genes of human THP-1 macrophages were measured. RESULTS: Periodontal treatment decreased the local inflammation in the periodontium, but did not have a significant effect on C-reactive protein (CRP) levels, VLDL composition, or VLDL potential to induce cholesterol uptake or gene expression by the macrophages. Incubation of macrophages in the presence of VLDL resulted in more than twofold increase in their cellular cholesterol content. Uptake of VLDL with ensuing macrophage cholesterol accumulation correlated positively with VLDL-associated lipopolysaccharide (LPS) activity (r=0.436, P=.016) and apolipoprotein E content (r=0.374, P=.046). Pre-treatment VLDL derived from the patients with high CRP levels displayed higher LPS activity than that of VLDL derived from patients with low CRP (above vs. below median, P=.007). In addition, pre-treatment VLDL isolated from patients with high systemic inflammation induced higher relative mRNA expression of CD14, TNF-α, MCP-1, and IL-6 in the macrophages. CONCLUSION: Inflammation and endotoxemia induced by severe periodontitis may increase VLDL-dependent macrophage activation and cellular cholesterol accumulation, and thereby atherogenesis.
Metabolism: clinical and experimental 12/2012; · 2.59 Impact Factor
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ABSTRACT: Background: Extracellular matrix-degrading proteinases are upregulated in atherosclerotic lesions and can contribute to subsequent pathological events. In the present nested case-control study, we investigated the association of serum concentrations of matrix metalloproteinases MMP-7, MMP-8, and MMP-13, tissue inhibitor of metalloproteinase-1 (TIMP-1), and neutrophil elastase (NE) with incident cardiovascular disease (CVD) events.Design: The FINRISK97 cohort included 8090 persons with no history of CVD. During the 10-year follow up, 471 incident CVD cases were ascertained and for them, three individually matched controls (n = 1413) were selected. The CVD events included myocardial infarction, stroke, coronary revascularization, and CVD death.Results: Compared to the controls, the cases had significantly higher serum mean concentrations of MMP-7, MMP-8, and TIMP-1, as well as MMP-7/TIMP-1 ratio. In multivariate analyses adjusted for CVD risk factors, MMP-7, MMP-8, TIMP-1, and MMP-8/TIMP-1 ratio were associated with the risk for incident CVD: OR 1.16 (95% CI 1.03-1.31), OR 1.13 (95% CI 1.01-1.26), OR 1.16 (95% CI 1.02-1.31), and OR 1.13 (95% CI 1.00-1.27) respectively, per SD-increase of log-transformed unit. The associations, however, attenuated into non-significant after adjusting for C-reactive protein (CRP) concentrations.Conclusions: MMP-7 and MMP-8, which are upregulated during inflammation, can form a proinflammatory tissue destructive cascade. They can be regarded as risk factors, and thus as potential biomarkers for incident CVD. The balance between these MMPs and their tissue inhibitor may indicate vulnerability to plaque rupture.
European journal of preventive cardiology. 10/2012;
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ABSTRACT: AIM: Type I collagen degradation end-products and related matrix metalloproteinases (MMPs) were examined aiming to detect potential markers of periodontitis in saliva, with high sensitivity and specificity. MATERIALS AND METHODS: The salivary concentrations of MMP-8, MMP-9 and MMP-13, tartrate-resistant acid phosphatase serum type 5b, C-terminal cross-linked telopeptide of type I collagen (CTx), N-terminal cross-linked telopeptide of type I collagen (NTx) and cross-linked carboxyterminal telopeptide of type I collagen were analysed in 230 subjects. Oral health examination included panoramic radiography. RESULTS: The concentrations of MMP-8, MMP-9 and MMP-13 in saliva were higher in subjects with generalized periodontitis than in controls. Of the tested salivary markers, MMP-8 was the only marker capable of differentiating subjects with severe alveolar bone loss from those with slight bone loss (p < 0.001). The association between the salivary MMP-8 levels and periodontitis remained significant after the adjustment with age, gender and smoking. In addition, significant correlations were found between the tested markers and periodontal parameters. CONCLUSION: Enzymes and end-products of type I collagen degradation have different associations with each other and with periodontal status that may reflect their roles in the cascade leading to alveolar bone loss. MMP-8 is a strong biomarker candidate for detecting alveolar bone destruction.
Journal Of Clinical Periodontology 09/2012; · 3.00 Impact Factor
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ABSTRACT: Bacterial endotoxins have been associated with chronic inflammation and the development and progression of diabetic nephropathy. We hypothesized that subjects with high serum lipopolysaccharide activity also carry remains of bacterial DNA in their system. Serum-derived bacterial DNA clones were isolated and identified from 10 healthy controls and 14 patients with type 1 diabetes (T1D) using universal primers targeted to bacterial 16S rDNA. A total of 240 clones representing 35 unique bacterial species were isolated and identified. A significant proportion of the isolated bacteria could be assigned to our living environment. Proteobacteria was by far the most prevalent phylum among the samples. Notably, the patients had significantly higher frequencies of Stenotrophomonas maltophilia clones in their sera compared to the healthy controls. Real-time PCR analysis of S. maltophilia and Pseudomonas aeruginosa flagellin gene copy number in the human leukocyte DNA fraction revealed that the overall Pseudomonal bacterial load was higher in older patients with T1D. Serum IgA- and IgG-antibody levels against Pseudomonal bacteria Delftia acidovorans, P. aeruginosa, and S. maltophilia were also determined in 200 healthy controls and 200 patients with T1D. The patients had significantly higher serum levels of IgA antibodies against all three Pseudomonal bacteria. Additionally, the IgA antibodies against Pseudomonal bacteria correlated significantly with serum C-reactive protein. These findings indicate that recurrent or chronic Pseudomonal exposure may increase susceptibility to chronic inflammation in patients with T1D.
Acta Diabetologica 08/2012; · 2.78 Impact Factor
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ABSTRACT: The aim of this study was to investigate the association between angiographically verified coronary artery disease (CAD) and salivary levels of four major periodontal pathogens.
The study population (n = 492) was composed of 179 (36.4%) patients with stable CAD, 166 (33.7%) with acute coronary syndrome (ACS), and 119 (24.2%) showing no pathological findings by coronary angiography. All patients were subjected to a detailed oral health examination. The saliva samples were analyzed for lipopolysaccharide activity as well as for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia by quantitative PCR. Serum antibodies levels against A. actinomycetemcomitans were analyzed.
The level of bacterial burden was linearly associated with alveolar bone loss (p < 0.001) and bleeding on probing (p = 0.015). The median salivary levels of A. actinomycetemcomitans in pathogen-positive patients were significantly higher in the "Stable CAD" (p = 0.014) and the "ACS" (p = 0.044) groups when compared to "No significant CAD" patients. In logistic regression models, a 10-fold increase in the salivary A. actinomycetemcomitans levels was associated with a risk for stable CAD and ACS with odds ratios (ORs) of 7.47 (95% confidence interval [CI]: 1.57-35.5, p = 0.012) and 4.31 (95% CI: 1.06-17.5, p = 0.041), respectively. The OR for the association of IgA-class antibody levels against A. actinomycetemcomitans with ACS risk was 3.13 (95% CI: 1.38-7.12, p = 0.006)/log(10) unit increase.
High salivary levels of A. actinomycetemcomitans and systemic exposure to the bacterium were associated with increased risk for CAD. These findings emphasize the importance of oral microbiota in cardiovascular risk assessment and therapeutics.
Atherosclerosis 05/2012; 223(2):478-84. · 3.79 Impact Factor
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ABSTRACT: An association exists between chronic infection-induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-8, tissue inhibitor of metalloproteinase (TIMP)-1 concentrations and MMP-8/TIMP-1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1-year follow-up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1-3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277-4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600-7.831; P = 0.002) and 2.87 (1.171-7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP-8/TIMP-1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295-8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.
Scandinavian Journal of Immunology 04/2012; 76(2):181-7. · 2.23 Impact Factor
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ABSTRACT: Purpose. The aim was to examine the relation of selected systemic and oral health parameters and the salivary presence of six periodontal pathogens to age-related macular degeneration (AMD). Methods. The present cross-sectional study includes data on 1,751 subjects (age ≥30 years). General health information was obtained by questionnaires and interviews, including self-reported diagnosis of AMD, as well as by the general and oral health examination, including panoramic radiography and laboratory analyses. Fifty-four subjects with degenerative fundus changes formed the AMD group, other 1697 formed the non-AMD group. Pearson's Chi-square and ANOVA tests were used for comparisons of categorical parameters and continuous parameters between the subject groups, respectively. A logistic regression analysis was performed to study the association of AMD with alveolar bone loss and the number of teeth by controlling for the age, diabetic status, systolic blood pressure, education, and smoking, and further for the carriage of salivary bacteria. Results. Advanced age, systolic blood pressure, and diabetes were associated with AMD (p<0.001), while the carriage rates of the examined periodontal pathogens were not. In the whole study population, the subjects with AMD had fewer teeth (p<0.001) and more alveolar bone loss (p=0.004) compared to non-AMD subjects. In a logistic regression model adjusted for age, smoking, and diabetes, alveolar bone loss was associated with AMD in males with an OR of 4.3 (95% CI 1.3-14.6, p=0.013). Conclusion. In this population-based health survey, alveolar bone loss is independently associated with AMD in males.
Journal of Periodontology 03/2012; · 2.60 Impact Factor
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ABSTRACT: BACKGROUND: Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. METHODS: The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6years. RESULTS: MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p<0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p<0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p<0.001) and 4.69 (1.10-20.01, p=0.037), respectively. CONCLUSIONS: The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics.
International journal of cardiology 01/2012; · 7.08 Impact Factor
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ABSTRACT: We investigated the association of periodontitis and severity of coronary artery disease (CAD) as verified using coronary angiography.
Participants were recruited among those attending coronary angiography at Helsinki University Central Hospital, Finland, in 2007 and 2008. Detailed clinical periodontal examination [number of teeth, bleeding on probing, periodontal probing depth (PPD)] and oral panoramic radiographs [alveolar bone loss (ABL), angular bone defects] were performed.
Of 506 patients, 123 (24.3%) had no significant CAD, whereas 184 (36.4%) had stable CAD and 169 (33.4%) acute coronary syndrome (ACS). Both stable CAD and ACS were associated with 8-17 missing teeth with ORs 4.33 (1.61-11.7, p = 0.020) and 5.24 (1.90-14.5, p = 0.014), and more than seven teeth with PPD ≥6 mm with ORs 2.44 (1.01-6.07, p = 0.049) and 2.75 (1.16-6.53, p = 0.022) respectively. Severe ABL was associated with ACS with an OR 5.39 (1.23-23.6, p = 0.025). Number of stenosed arteries was linearly associated with ABL (p for trend <0.001), number of missing teeth (p < 0.001), and pockets with probing depth ≥6 mm (p = 0.033).
Compared with patients with no significant stenosis, poor periodontal health including missing teeth, periodontal inflammation, and bone loss is associated with angiographically verified coronary artery narrowing in patients with stable CAD or ACS.
Journal Of Clinical Periodontology 11/2011; 38(11):1007-14. · 3.00 Impact Factor
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ABSTRACT: Arterial disease is associated with elevated serum matrix metalloproteinase (MMP)-8 concentration. We studied the role of two promoter region single nucleotide polymorphisms (SNPs) of MMP-8 gene in the arterial disease. The population comprised patients with arterial disease (n = 124) and healthy blood donors (n = 100) as a reference group for MMP-8 SNPs (-799C/T and -381A/G) genotypes and serum concentrations. Genotype frequencies for MMP-8 -799C/T SNP in arterial disease were C/C (43.5%), C/T (32.3%) and T/T (24.2%), and in the reference group they were C/C (50.0%), C/T (40.0%) and T/T (10.0%; P = 0.012). The -799C allele frequency was lower in the patients (59.7%) than in the reference group (70.0%; P = 0.023). The -799C allele showed protective effects against the arterial disease with an odds ratio [95% confidence interval (CI)] of 0.372 (0.141-0.980, P = 0.045) after adjustment for age, gender, and serum MMP-8 and TIMP-1 concentrations. Only in the reference group and whole study population (n = 224), the -799TT genotype significantly associated with an increase in serum MMP-8 concentrations (P = 0.047, 0.025). The -799C allele appeared protective against the arterial disease. The genotype may have an effect on systemic MMP-8 levels which could not, however, be seen in the arterial disease patients probably as a result of the strong inflammation involved in the disease pathogenesis.
Innate Immunity 10/2011; 18(3):511-7. · 4.00 Impact Factor
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ABSTRACT: Sorsa T, Mäntylä P, Tervahartiala T, Pussinen PJ, Gamonal J, Hernandez M. MMP activation in diagnostics of periodontitis and systemic inflammation. J Clin Peridontol 2011; doi: 10.1111/j.1600-051X.2011.01753.x.
Journal Of Clinical Periodontology 06/2011; 38(9):817-9. · 3.00 Impact Factor
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ABSTRACT: Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross-reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (n = 141) were monitored at baseline when entering to hospital, and after 1 week, 3 months and 1 year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow-up. Serum IgG-class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r∼0.4, P < 0.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG- and IgA-seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non-carriers. HSP60 antibody levels did not differ significantly between the edentulous, non-periodontitis and periodontitis patients. Despite the observed cross-reactivity in the systemic IgG-class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.
Scandinavian Journal of Immunology 06/2011; 74(4):383-9. · 2.23 Impact Factor
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International Journal of Epidemiology 06/2011; 41(5):1265-71. · 6.41 Impact Factor
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Mariann I Lassenius,
Kirsi H Pietiläinen,
Kati Kaartinen, Pirkko J Pussinen,
Jaana Syrjänen,
Carol Forsblom,
Ilkka Pörsti,
Aila Rissanen,
Jaakko Kaprio,
Jukka Mustonen,
Per-Henrik Groop,
Markku Lehto
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ABSTRACT: To investigate whether bacterial lipopolysaccharide (LPS) activity in human serum is associated with the components of the metabolic syndrome (MetS) in type 1 diabetic patients with various degrees of kidney disease and patients with IgA glomerulonephritis (IgAGN).
Serum LPS activity was determined with the Limulus Amoebocyte Lysate chromogenic end point assay in type 1 diabetic patients with a normal albumin excretion rate (n = 587), microalbuminuria (n = 144), macroalbuminuria (n = 173); patients with IgAGN (n = 98); and in nondiabetic control subjects (n = 345). The relationships of the LPS/HDL ratio and MetS-associated variables were evaluated with Pearson correlation.
The MetS was more prevalent in type 1 diabetic patients (48%) than in patients with IgAGN (15%). Diabetic patients with macroalbuminuria had a significantly higher serum LPS/HDL ratio than patients with IgAGN. In the normoalbuminuric type 1 diabetic group, patients in the highest LPS/HDL quartile were diagnosed as having the MetS three times more frequently than patients in the lowest quartile (69 vs. 22%; P < 0.001). High LPS activity was associated with higher serum triglyceride concentration, earlier onset of diabetes, increased diastolic blood pressure, and elevated urinary excretion of monocyte chemoattractant protein-1.
High serum LPS activity is strongly associated with the components of the MetS. Diabetic patients with kidney disease seem to be more susceptible to metabolic endotoxemia than patients with IgAGN. Bacterial endotoxins may thus play an important role in the development of the metabolic and vascular abnormalities commonly seen in obesity and diabetes-related diseases.
Diabetes care 06/2011; 34(8):1809-15. · 8.09 Impact Factor
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ABSTRACT: Pathogens such as Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) associate with an increased risk for cardiovascular diseases by inducing inflammation. We hypothesized that the pathogens affect the vascular wall by disturbing cholesterol homeostasis and endothelial function.
Aa- and Cpn-infections were induced in apoE-deficient mice by intravenous and intranasal applications, respectively. Cholesterol efflux from mouse peritoneal macrophages to apo(lipoprotein)A-I was assessed. The efflux capacity of mouse sera as acceptors of cholesterol from RAW264.7-macrophages was determined. Additionally, endothelial function was studied by following the relaxation capacity of rat mesenteric arteries after incubation in the conditioned culture media of the peritoneal macrophages isolated from the mice.
Infection increased serum phospholipid transfer protein (PLTP) and lipopolysaccharide (LPS) activity, as well as serum amyloid A (SAA) and TNF-α concentrations. Peritoneal macrophages of mice with Aa-infection showed increased cholesterol uptake and reduced cholesterol efflux. Sera of Cpn and Cpn + Aa-infected mice had reduced cholesterol efflux capacity from RAW264.7-macrophages. Conditioned macrophage medium from mice with chronic C. pneumoniae infection induced endothelial dysfunction. Additionally, concentrations of serum adhesion molecules, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in Cpn-groups and E-selectin in Cpn + Aa-group, were elevated. The serum markers of endothelial function correlated positively with SAA.
Aa- and Cpn-infections may generate proatherogenic changes in the vascular wall by affecting the macrophage cholesterol homeostasis and endothelial function.
Microbial Pathogenesis 03/2011; 51(3):217-24. · 1.94 Impact Factor
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ABSTRACT: We investigated in a nationally representative sample, how periodontitis modifies the association between the carriage of periodontal pathogens and serology.
The population comprised 1586 dentate subjects who participated in an interview, clinical and radiological oral health examination, and saliva collection. Serum immunoglobulin A (IgA)- and IgG-class antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and their salivary occurrence were determined in the whole population. The quantity of the pathogens was measured in a subpopulation.
In the univariate analyses, the corresponding antibody levels were higher in the pathogen carriers compared with the non-carriers, and clearly higher in the carriers with periodontal pockets compared with the carriers without. In the multi-variate analyses, however, all antibody levels associated strongly with age (p<0.001) and the carriage of the corresponding pathogen (p<0.001), but only weakly with the presence or number of teeth with periodontal pockets. In the subpopulation, the antibody levels and the numbers of corresponding bacteria in saliva had a positive association, which was not affected by the disease.
The carriage of A. actinomycetemcomitans and P. gingivalis is the strongest determinant of the systemic antibody response to these pathogens, and the extent of periodontitis has at most a modest modifying effect.
Journal Of Clinical Periodontology 03/2011; 38(5):405-11. · 3.00 Impact Factor
