Periodontal condition in Japanese coronary heart disease patients: A comparison between coronary and non-coronary heart diseases.

OBJECTIVE: The aim of this clinical trial was to assess the relationship between periodontal bacterial burden and coronary heart disease (CHD) in Japanese population. BACKGROUND: Many epidemiological reports suggest that periodontitis is a risk factor for CHD; however, the influence of each periodontal bacterium and periodontal condition in Japanese CHD patients is unclear. METHODS: We studied 897 patients with cardiovascular diseases in Tokyo Medical and Dental University Hospital from May 2012 to August 2015. The subjects were divided into six groups according to age and the existence of CHD (46-60 years with CHD (n = 56): Group YC, 61-70 years with CHD (n = 106): Group MC, over 70 years with CHD (n = 177): Group EC, 46-60 years without CHD (n = 152): Group YN, 61-70 years without CHD (n = 216): Group MN, and over 70 years without CHD (n = 190): Group EN). RESULTS: We found that the patients in Groups MC and EC had deeper periodontal pocket compared to the patients in Group YN (P < 0.05), although there was no statistical difference of pocket depth between Group YC and Groups MC and EC. Many subjects in Group EC had high anti-Porphyromonas gingivalis and anti-Prevotella intermedia antibodies in comparison to Group EN (P < 0.05). The CHD patients generally had worse oral condition than the non-CHD patients. Elderly with CHD had a higher level of serum anti-Porphyromonas gingivalis antibody and anti-Prevotella intermedia antibody than those without CHD. CONCLUSION: Increased periodontal infection was found in Japanese CHD patients compared to non-CHD patients.

Level of serum antibody against a periodontal pathogen is associated with atherosclerosis and hypertension.

Inflammation has a role in the pathogenesis of atherosclerosis, which causes hypertension. Results from some studies have suggested links between periodontal disease and atherosclerosis, but links between periodontal disease and hypertension have been seldom studied. We investigated whether periodontal disease and serum antibody level were associated with hypertension. We studied 127 patients (93 men and 34 women, mean age 68±9 years) who were admitted with ischemic heart disease to our institution. A composite periodontal risk score was calculated from five periodontal vector scores. The levels of serum antibody against Porphyromonas gingivalis (Pg) were measured. Pulse pressure, mean blood pressure (BP) and pulse wave velocity were used as indices of atherosclerosis. We divided patients into two groups according to the levels of serum antibody against Pg: higher or equal to the median (high Pg antibody group) and lower than the median (low Pg antibody group).There was no difference in the use of antihypertensive agents between the two groups. The composite periodontal risk score (P=0.0003), systolic BP (P=0.030), diastolic BP (P=0.038), pulse pressure (P=0.050) and mean BP (P=0.055) were higher in the high Pg antibody group than in the low Pg antibody group. The composite periodontal risk score (r=0.320, P=0.0003), systolic BP (r=0.212, P=0.017), diastolic BP (r=0.188, P=0.035) and mean BP (r=0.225, P=0.011) correlated with the level of serum antibody against Pg, even after adjustment for age. An elevated antibody level against Pg indicates advanced periodontal disease and suggests advancement of atherosclerosis and hypertension.

Association of serum anti-periodontal pathogen antibody with ischemic stroke.

BACKGROUND: Periodontitis increases the risk of atherosclerotic cardiovascular disease and ischemic stroke. In this study, we evaluated whether serum antibody levels against individual periodontal pathogens are significantly associated with ischemic stroke subtypes and their risk factors. METHODS: Patients with acute ischemic stroke (n = 132; 74 male and 58 female, 71.3 ± 10.7 years) and patients with no previous stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. Stroke subtype was evaluated based on the Trial of Org 10172 in Acute Stroke Treatment classification. Serum was obtained from each patient after obtaining their consent to participate in the study. The levels of serum antibodies against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi) were evaluated by ELISA. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured by nephelometry. RESULTS: Serum hs-CRP levels were significantly associated with acute ischemic stroke even after controlling for acute ischemic stroke, hypertension, diabetes mellitus and bulb/ internal carotid artery (ICA) atherosclerosis which were statistically selected (coefficient 0.245, 95% CI 0.142-0.347, p < 0.0001). The serum-antibody level of Pi was significantly higher in atherothrombotic-stroke patients than in patients with no previous stroke (p = 0.0035). Detectable serum anti-Pg antibody was significantly associated with atrial fibrillation (overall χ(2) = 35.5, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 4.36, 95% CI 1.71-12.10, p = 0.0017), and detectable serum anti-Pi antibody was significantly associated with bulb/ICA atherosclerosis after controlling for the statistically selected associated factors (overall χ(2) = 46.1, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 16.58, 95% CI 3.96-78.93, p < 0.0001). The levels of serum anti-Pi antibody were significantly associated with atherothrombotic stroke with the statistically selected associated factors excluding bulb/ICA atherosclerosis (overall χ(2) = 77.0, R(2) = 0.44, n = 129, p < 0.0001; anti-Pi antibody: OR 23.6, 95% CI 2.65-298.2, p = 0.008). However, when we included bulb/ICA atherosclerosis in this model, the levels of serum anti-Pi antibody were no longer significantly associated with atherothrombotic stroke (overall χ(2) = 98.0, R(2) = 0.56, n = 129, p < 0.0001; anti-Pi antibody: p = 0.107). CONCLUSIONS: Our results suggest that anti-Pg antibody is associated with atrial fibrillation and that anti-Pi antibody is associated with carotid artery atherosclerosis. In addition, anti-Pi antibody may be associated with atherothrombotic stroke through its association with carotid artery atherosclerosis. Thus, periodontitis may lead to serious systemic diseases.

Significant association between score of periodontal disease and coronary artery disease.

Recently, several researchers have demonstrated the association between periodontal disease and coronary artery disease (CAD). Therefore, we herein investigate the association between periodontal diseases and the existence of CAD among the study population who received both coronary angiography and dental examination. A total of 174 consecutive patients with dental examination including radiography and coronary angiography in the same hospitalization were recruited (64.5 +/- 10.3 years, M/F: 94/80). A dentist assessed severity of periodontal status markers (bleeding on probing, probing depth >or=6 mm, teeth lost, alveolar bone resorption >half of root length by radiography and smoking status). We divided these patients into two groups according to whether they had CAD (CAD group, n = 99) or not (non-CAD group, n = 75) according to the results of coronary angiography. The composite periodontal risk scores calculated from periodontal status markers were higher in the CAD group than in the non-CAD group (P = 0.02). The composite periodontal scores were higher in the CAD group of age <60 years old population (P = 0.03) and in the CAD group of patients with normal glucose tolerance (P = 0.04). However, the difference was not significant in the age >or=60 years old population or those with diabetes mellitus or impaired glucose tolerance. In all populations, hypertension, glucose tolerance, statin therapy, and composite of periodontal risk scores were associated with CAD. Multivariate analyses revealed statin therapy, glucose tolerance, and periodontal risk scores were independent and significant risk factors for CAD. Composite periodontal risk scores were independent and significant predictive factors for CAD.

Periodontal status and Prevotella intermedia antibody in acute coronary syndrome.

We performed periodontal examination and measured serum antibody levels against Prevotella intermedia in patients with acute coronary syndrome (ACS). Composite periodontal risk scores were significantly higher in the ACS group than in the coronary artery disease (CAD) group. Serum antibody levels were higher in the ACS group than in the CAD group and those were significantly correlated with the composite periodontal risk scores. These results provided important information about the status of P. intermedia infection in patients with ACS.

Vascular endothelial growth factor reduces Fas-mediated acute liver injury in mice.

BACKGROUND AND AIM: Fulminant hepatitis is still a fatal liver disease, and no specific treatment for it has been available. Vascular endothelial growth factor (VEGF) is the focus of attention because of its various actions. We investigated the effect of vascular endothelial growth factor (VEGF) on Fas-induced fulminant hepatic failure (FHF). METHOD: Male Balb/c mice were treated with an intraperitoneal injection of an anti-Fas antibody (Jo-2 Ab) with or without premedication with intraperitoneally administered human recombinant VEGF. RESULTS: The serum level of alanine aminotransferase (ALT) was up to 300 times higher that of normal mice following the Jo-2 Ab injection, and histological analysis revealed hepatic injury and massive hepatocyte apoptosis. The VEGF significantly suppressed an elevation in serum ALT levels and hepatocyte apoptosis. Immunohistochemically, VEGF-treated mice showed that Bcl-xL in hepatocytes was strongly expressed. CONCLUSIONS: Since hepatocytes do not express VEGF receptors, we speculated that VEGF acts on sinusoidal endothelial cells (SECs) and promotes production of cytokines such as hepatocyte growth factor in SECs, resulting in reducing apoptosis through an increase expression of Bcl-xL in hepatocytes. We suggest that VEGF has a potent antiapoptotic effect on hepatocytes through cell-cell interaction between SECs and hepatocytes.

Human lactiferous mammary gland cells produce vascular endothelial growth factor (VEGF) and express the VEGF receptors, Flt-1 AND KDR/Flk-1.

Human milk contains a variety of growth factors. Recently, it was reported that vascular endothelial growth factor (VEGF) was one of them. We investigated milk VEGF isoforms, their functions, and VEGF receptors on mammary gland epithelial cells (MEC). The VEGF concentration in human milk was 74.3+/-34.9ng/ml on the first day after delivery, and rapidly decreased in a couple of days to 6.2+/-2.3ng/ml on the fifth day, and matured milk maintained about 4ng/ml. In an MTT assay, human milk accelerated HUVEC proliferation and MV303, a neutralizing antibody of VEGF, blocked 17.3 % of the effect. Immunoprecipitation and Western blotting showed that VEGF121 and VEGF165 were contained in human colostrums, and RT-PCR of human MEC confirmed that VEGF121, VEGF165 and VEGF189 were present. By immunostaining of human breast tissues, RT-PCR of MEC from human colostrum and measurement of the VEGF concentrations of conditioned media of cultured human MEC, it was confirmed that VEGF was produced by MEC. MEC was also expressed VEGF receptors, flt-1 and Flk-1/KDR. These results speculate us that the existence of autocrine or paracrine system within breast tissue via VEGF receptors on MEC and have a role in lactation.

Ratio of serum vascular endothelial growth factor to platelet count correlates with disease activity in a patient with POEMS syndrome.

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of POEMS (polyneuropathy, organomegaly, endocrine disorder, M-protein, and skin lesion) syndrome. Because platelets have recently been recognized as transporters of VEGF, enhanced blood coagulation activity in this syndrome may accelerate vasopermeability by releasing VEGF from platelets in vivo. Here we report a case of POEMS syndrome with anasarca showing a high ratio of serum VEGF to platelet count, indicative of massive VEGF release from aggregated platelets in vivo. Changes in the ratio clearly reflected disease activity. This observation suggests that the ratio of serum VEGF to platelet count is more precise in monitoring disease activity than serum VEGF alone, and that VEGF released in vivo is critically involved in the pathogenesis of POEMS syndrome, causing hypervasopermeability.