PAI-1 and TNF-alpha profiles of adipose tissue in obese cardiovascular disease patients

Obesity as a leading preventable cause of death worldwide is closely linked to cardiovascular disease (CVD). Plasma plasminogen activator inhibitor (PAI)-1, a potent inhibitor of plasminogen activation and fibrinolysis, is increased in many clinical situations associated with high incidence of CVD. In the obesity-linked elevation of PAI-1, evidence points to TNF-alpha as an important regulator of PAI-1 expression in adipose tissue. Background: This study aims to evaluate mediastinal PAI-1 and TNF-alpha mRNA levels in adipose tissues (AT) and compare serum levels in obesity with and without coronary artery disease (CAD). Patients and methods: Obese patients with (n=37) and without CAD (n=20) were included in the study. Results: The serum levels of PAI-1 and TNF-alpha were significantly higher in obese patients with CAD compared to obese patients without CAD. PAI-1 mRNA expression was significantly increased in mediastinal adipose tissue (MAT) of obese patients with CAD compared to those without CAD, TNF-alpha mRNA expressions were found to be higher in EAT (epicardial AT), MAT and SAT (subcutaneous AT) of obese patients with CAD. Conclusions: The study demonstrated a close direct relationship between TNF-alpha and PAI-1. PAI-1 mRNA expression strongly correlated positively with serum TNF-alpha in MAT, and TNF-alpha expressions with PAI-1 serum levels

Inhaled corticosteroids' effects on biomarkers in exhaled breath condensate and blood in patients newly diagnosed with asthma who smoke

Objective Exposure to cigarette smoke complicates the treatment and management of asthma through a variety of inflammatory effects. This study aimed to investigate the differences between newly diagnosed cases of asthma in smokers and nonsmokers in terms of localized and systemic biomarkers following treatment with inhaled corticosteroids (ICS) or ICS in combination with a long-acting beta 2 agonist (LABA). Methods Specimens of exhaled breath condensate (EBC) from newly diagnosed patients with asthma were used to quantify inflammation in the airways, while blood samples were used to assess systemic inflammation. In both samples, the levels of IL-6, LTB4, LTD4, and 8-isoprostane were measured and these were repeated after 3 months of treatment with ICS or ICS + LABA. Results Of the 20 patients, 10 (50%) were nonsmokers with asthma (NSA) and 10 (50%) smokers with asthma (SA). There was no statistically significant difference in the blood or EBC levels of IL-6, LTB4, LTD4, or 8-isoprostane between the groups prior to treatment. Only the decrease in 8-isoprostane level in the EBC samples was found to be significantly greater in the NSA group after treatment (for smokers, the change was 2.91 +/- 23.22, while for nonsmokers it was -22.72 +/- 33.12, p = 0.022). Post-treatment asthma control was significantly better in the NSA group (p = 0.033). Conclusion Monitoring the alterations in 8-isoprostane levels in EBC in patients with asthma who smoke may be helpful in deciding on therapeutic management and switching treatments. Asthma control was better in nonsmokers than in smokers

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Background: Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects

Mediastinal adipose tissue expresses a pathogenic profile of 11 beta-hydroxysteroid dehydrogenase Type 1, glucocorticoid receptor, and CD68 in patients with coronary artery disease

WOS: 000319639600002PubMed ID: 22955009Objective: Cardiac visceral fat is accepted to be a new marker for cardiometabolic risk due to its association with increased cardiovascular risk factors. This study aimed to compare the expression of 11 beta hydroxysteroid dehydrogenases (11 beta-HSD)-1, glucocorticoid receptor (GCR), and CD68 in mediastinal and subcutaneous adipose tissues (MAT, and SAT, respectively) and to assess their possible relationships with the development of coronary artery disease (CAD). Methods and results: Expression of 11 beta-HSD-1, GCR, and CD68 mRNA levels were measured by quantitative real-time polymerase chain reaction in MAT and SAT tissues of 37 patients undergoing coronary artery bypass grafting due to CAD (CAD group) and 19 non-CAD patients (controls) undergoing heart valve surgery. 11 beta-HSD-1 in MAT and SAT and GCR expression in MAT and SAT were found to be significantly increased in CAD group when compared with controls (P<.05, respectively). In CAD group, 11 beta-HSD-1 mRNA levels were found to be significantly higher in MAT compared to SAT (P<.05). CD68 mRNA levels were significantly higher in MAT of CAD group compared to controls (P<.05). Immunohistochemical analyses demonstrated the presence of CD68+ cells and increased 11 beta-HSD-1 expression in MAT of CAD group compared to SAT. Conclusion: The present study demonstrate that the mediastinal fat exhibits a pathogenic mRNA profile of 11 beta-HSD-1, GCR, and CD68. The identification of 11 beta-HSD-1 expression within the mediastinal fat, along with increased GCR expressions and the presence of CD68+ cells highlight that MAT potentially contributes to the pathogenesis of CAD. (C) 2013 Elsevier Inc. All rights reserved.Turkish Diabetes Foundation; Sanovel Pharmaceuticals CompanyThis study was funded by Turkish Diabetes Foundation and Sanovel Pharmaceuticals Company