Intriguingly, constrictive remodeling and neointimal formation were both similarly most exacerbated in the case of the n/i/eNOS(-/-) bone marrow selleck products transplantation. These results indicate that the complete disruption of all the NOS genes causes markedly accelerated vascular lesion formation caused by blood flow disruption in mice in vivo, demonstrating the crucial vasculoprotective role of the whole endogenous NOS system. Our findings also suggest that the NOS system in bone marrow-derived cells may be involved in this vasculoprotective mechanism. (C) 2011 Elsevier Inc. All rights reserved.”
“Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation.

S-Nitroso-N-acetylcysteine (SNAC),

a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain APR-246 purchase unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100 mu M) or vehicle (control group) for 72 h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGF beta-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion

of myofibroblast-like PIK-5 phenotype into quiescent cells. SNAC decreased gene and protein expression of TGF beta-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis. (C) 2011 Elsevier Inc. All rights reserved.”
“Nitric oxide and secondary oxides of nitrogen react with unsaturated fatty acids such as linoleic acid to yield oxidized and nitrated products. Fatty acid nitroalkene derivatives, (e.g. nitrolinoleate [LNO(2)]) are produced by oxidative inflammatory reactions, detected clinically, display potent electrophilic reactivity and induce post-translational protein modifications that mediate adaptive inflammatory signaling responses. LNO(2) signaling was examined in lung epithelial cells because the alveolar compartment is a rich site for the transduction of redox and inflammatory reactions. LNO(2) did not directly induce Ca(2+) influx in cultured lung epithelial cells, but inhibited bradykinin-induced Ca(2+) influx in a cGMP-independent manner.