Periodontitis induces endothelial dysfunction in mice.

The treatment of periodontitis has numerous positive effects on established chronic health conditions, including cardiovascular disease and diabetes. However, ethical considerations do limit the establishment of human trials to investigate whether periodontitis promotes the early stages of chronic conditions. Therefore, the aim of this study was to investigate whether periodontitis induces endothelial dysfunction in hyperlipidemic apolipoprotein E gene-deficient (ApoE-/-) mice. Forty-five 8-week-old ApoE-/- mice were challenged by oral lavage with Porphyromonas gingivalis and Streptococcus gordonii for 4 weeks. A subgroup of animals (n = 15-17/group) was placed in a metabolic chamber immediately before euthanasia at 4 weeks to measure VO2/CO2 concentrations and voluntary locomotion. In infected and control animals alveolar bone levels were measured by x-ray imaging and endothelial function was determined by measuring endothelial-dependent vasorelaxation of aortic rings. The mRNA expression levels of serum amyloid A and tumor necrosis factor were determined in liver tissues by qRT PCR and protein concentrations in serum by ELISA. Caecal contents were analysed by sequencing to determine changes to the gut microbiota to investigate linkages between microbiome and systemic changes. The results showed that oral lavage of P. gingivalis and S. gordonii for 4 weeks, initiated periodontitis in ApoE-/- mice, similar to the human situation. The oral inflammation was accompanied by a significant increase in mRNA expression of pro-inflammatory mediators serum amyloid A1 and tumor necrosis factor in the liver. Mice with periodontitis also exhibited impaired endothelial-dependent vasorelaxation responses to acetylcholine. This systemic response was connected to increased energy expenditure, locomotion and respiratory quotient. No differences were detected in caecal microbiota between the infected and control animals. Overall, this is the first report that provide evidence that periodontitis induces endothelial dysfunction in mice. Other systemic responses observed in response to the local reaction need further investigation. The study suggests that early prevention of periodontitis may help limit the early stages of endothelial dysfunction that is linked to atherogenesis in humans.

Correlates of serum leptin and insulin-like growth factor-I concentrations in normal weight and overweight/obese Iranian women.

BACKGROUND: Leptin and insulin-like growth factor-I (IGF-I) are two interrelated hormones that are implicated in the development or progression of coronary artery disease (CAD) and some cancers. The aim of this study was to investigate the relation between serum leptin and total IGF-I concentrations and to identify their correlations with age or anthropometric and body composition variables in healthy normal weight and overweight/obese Iranian women. METHODS: The percent of body fat (BF%), fat mass (FM), fat-free mass (FFM), and waist/hip ratio (WHR) were determined in 51 healthy normal weight (body mass index [BMI] 18.5-24.9 kg/m(2)) and 50 overweight/obese (BMI > or = 25 kg/m(2)) Iranian reproductive-age women. Serum leptin and total IGF-I concentrations were measured by double-antibody sandwich assay and enzyme-linked immunosorbent assay (ELISA), respectively. Statistical analysis was performed by Mann-Whitney U test and Spearman's rank-correlation test. Multivariate linear regression analysis was performed with ranked-transformed data to obtain partial correlation coefficient. RESULTS: In this group of healthy, premenopausal Iranian women, variance of serum leptin concentration was independently explained by FM (partial rho = 0.295, p < 0.01), and variance of the total IGF-I concentration was explained by age (partial rho = -0.214, p = 0.037) and BMI (partial rho = 0.229, p = 0.026). Overweight/obese women had higher leptin and total IGF-I concentrations than normal weight women (p < 0.01). The serum leptin and total IGF-I concentrations were differentially correlated with age and anthropometric and body composition variables in the two groups. Whereas in normal weight women, leptin was negatively related to BMI (partial rho = -0.356, p = 0.015), in overweight/obese women, BMI, BF%, and FM independently contributed to the serum leptin variability (partial rho = 0.370, p = 0.013; partial rho = -0.320, p = 0.034; partial rho = 0.421, p < 0.01, respectively). There was a weak association between age and total IGF-I concentration in normal weight women, which did not reach statistical significance (partial rho = -0.255, p = 0.091). None of the variables was associated with the total IGF-I in overweight/obese women (p > 0.05). CONCLUSIONS: Although the studied anthropometric and body composition variables could explain approximately half of the leptin variance in Iranian women, they explained only a small proportion of total IGF-I variability. Our results indicated that the serum leptin and total IGF-I concentrations are differentially regulated in healthy normal weight and overweight/obese Iranian women.