Aim: Resveratrol (RSV) is an edible polyphenolic phytoalexin present in different plant species that plays an important role in improving endothelial dysfunction. However, the molecular mechanisms underlying these effects are unknown. In the present study, the mechanism underlying the protection of CRL-1730 cells by RSV against oxidative stress was examined. Methods: We first assessed the effects of RSV on the cell viability and apoptosis of CRL-1730 cells exposed to hydrogen peroxide (H2O2). Real-time PCR was used to determine the microRNA-126 (miR-126) expression in cells treated with RSV and/or H2O2. We also evaluated the PI3K/Akt signaling pathway in CRL-1730 cells following upregulation of the miR-126 expression. Finally, we determined the effects of miR-126 on RSV against oxidative injury using an miR-126 inhibitor. Results: Treatment with RSV resulted in a significant increase in survival and a decrease in the apoptosis of CRL-1730 cells exposed to H2O2. We also found that H2O2 significantly suppressed the expression of miR-126, which was reversed by RSV in a dose-dependent manner. The overexpression of miR-126 decreased PIK3R2 (p85-β) and enhanced Akt phosphorylation, which resulted in an increase in the survival of CRL-1730 cells exposed to H2O2. More importantly, the downregulation of the miR-126 expression reversed the effects of RSV on the survival and apoptosis of CRL-1730 cells exposed to H2O2. In addition, the knockdown of Ets-1 reversed the effects of RSV on the miR-126 expression in CRL-1730 cells exposed to H2O2. Conclusions:In this study, we demonstrated that the protection of endothelial cells by RSV against oxidative injury is due to the activation of PI3K/Akt by miR-126.

Zinc finger protein A20 is a key negative regulator of inflammation. However, whether A20 may affect inflammation during peritoneal dialysis (PD)-associated peritonitis is still unclear. This study was aimed to investigate the effect of A20 overexpression on lipopolysaccharide (LPS)-induced inflammatory response in rat peritoneal mesothelial cells (RPMCs). Isolated and cultured RPMCs in vitro. Plasmid pGEM-T easy-A20 was transfected into RPMCs by Lipofectamine™2000. The protein expression of A20, phospho-IκBα, IκBα, TNF receptor-associated factor (TRAF) 6 and CD40 were analyzed by Western blot. The mRNA expression of TRAF6, CD40, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real time-PCR. NF-κB p65 DNA binding activity, IL-6 and TNF-α levels in cells culture supernatant were determined by ELISA. Our results revealed that RPMCs overexpression of A20 lead to significant decrease of LPS-induced IκBα phosphorylation and NF-κB DNA binding activity (all p < 0.01). In addition, A20 also attenuated the expression of TRAF6, CD40, IL-6 and TNF-α as well as levels of IL-6 and TNF-α in cells culture supernatant (all p < 0.05). However, A20 only partly inhibited CD40 expression. Our study indicated that A20 overexpression may depress the inflammatory response induced by LPS in cultured RPMCs through negatively regulated the relevant function of adaptors in LPS signaling pathway.

BackgroundAtrialfibrillation (AF) is associated with the activation of the renin‐angiotensin‐aldosterone system in the atria. It is not clear whether the expression of a mineralocorticoid receptor (MR), or 11β‐hydroxysteroid dehydrogenase type 2 (11βHSD2), conferring aldosterone specificity to the MR, in patients with AF is altered.HypothesisPatients with AF may be associated with increased expression of MR and 11βHSD2 in the atria.MethodsAtrial tissue samples of 25 patients with rheumatic heart valve disease undergoing a valve replacement operation were examined. A total of 13 patients had chronic persistent AF (>6 mo) and 12 patients had no history of AF. The MR and 11βHSD2 expression were analyzed at the mRNA and protein level. The localization of MR and 11βHSD2 in atrial tissue was performed using specific immunohistochemistry staining.ResultsThe results of real‐time quantitative polymerase chain reaction (PCR) showed that AF groups, in comparison with sinus rhythm, had a higher mRNA expression level of MR or 11βHSD2 (all P < 0.01). Both the MR and 11βHSD2 protein expression level in atrial tissue were also significantly increased in patients with AF compared with patients with sinus rhythm (P < 0.05 or P < 0.01). The immunohistochemical staining of MR or 11βHSD2 demonstrated that MR and 11βHSD2 predominately located in the cytoplasm of myocardial cells in the atrium and the intensity and density of immunostaining appeared to be increased in the atria of patients with AF compared to those without AF.ConclusionsIncreasing expression of MR and 11βHSD2 in the atria during AF is one of the molecular mechanisms for development of atrial interstitial fibrosis in patients with AF. These findings may have an important impact on the treatment of AF with aldosterone antagonists. Copyright © 2010 Wiley Periodicals, Inc.

Increased expression of MR and CYPIIB2 in the atria is one of the molecular mechanisms for the development of atrial interstitial fibrosis in patients with atrial fibrillation.