ABSTRACT
BACKGROUND AND PURPOSE: Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown to inhibit cardiac fibrosis. However, the underlying mechanisms are poorly understood. We investigated the regulation by PPAR-gamma ligands of angiotensin (Ang) II-induced plasminogen activator inhibitor (PAI)-1, extracellular matrix (ECM) production and cell growth in cardiac fibroblasts. EXPERIMENTAL APPROACH: The effects of PPAR-gamma ligands on Ang II-induced PAI-1, ECM expression and cell growth were assessed in primary-cultured rat cardiac fibroblasts; cardiac PAI-1 and ECM production was examined in Ang II-infused rats. KEY RESULTS: In growth-arrested cardiac fibroblasts, PPAR-gamma ligands rosiglitazone and 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) dose-dependently attenuated Ang II-induced cell proliferation and expression of PAI-1, collagen type-I, collagen type-III and fibronectin. An accompanying increase in PPAR-gamma expression and activation was also observed. These suppressive effects were attenuated by the PPAR-gamma antagonists GW9662 and bisphenol A diglycidyl ether (BADGE). Moreover, rosiglitazone and 15d-PGJ2 inhibited in part the expression and phosphorylation of Ang II-induced transforming growth factor (TGF)-beta1, Smad2/3 and c-Jun NH(2)-terminal kinase (JNK). Ang II infusion in rats markedly increased left ventricular production of PAI-1, collagen and fibronectin, with a concurrent increase in the ratios of heart weight/body weight and left ventricle weight/body weight. Co-treatment with rosiglitazone significantly decreased these levels and upregulated PPAR-gamma expression. CONCLUSIONS AND IMPLICATIONS: Rosiglitazone and 15d-PGJ2 suppress Ang II-induced production of PAI-1 and ECM probably via interactions between PPAR-gamma and TGF-beta1/Smad2/3 and JNK signalling pathways. It is suggested that PPAR-gamma and its ligands may have potential applications in preventing cardiac fibrosis.
Subject(s)
Extracellular Matrix/drug effects , PPAR gamma/agonists , Plasminogen Activator Inhibitor 1/metabolism , Angiotensin II/pharmacology , Animals , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Extracellular Matrix/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibrosis/prevention & control , Gene Expression Regulation/drug effects , Male , Myocardium/cytology , Myocardium/metabolism , Prostaglandin D2/administration & dosage , Prostaglandin D2/analogs & derivatives , Prostaglandin D2/pharmacology , Rats , Rats, Sprague-Dawley , Rosiglitazone , Signal Transduction , Thiazolidinediones/administration & dosage , Thiazolidinediones/pharmacology , Transforming Growth Factor beta1/drug effects , Transforming Growth Factor beta1/metabolismABSTRACT
The catalytic incineration of dimethyl sulfide and dimethyl disulfide in a MnO/Fe(2)O(3) fixed bed catalytic reactor was studied. This paper provides information on the affect of the operating parameters that included: inlet temperature, space velocity, VOC concentration and O(2) concentration. The results show that the conversion of VOCs increases as the inlet temperature increases and the space velocity decreases. The higher the concentration of VOCs, the lower their conversions. The O(2) concentration has no affect on the conversion of VOCs. VOCs have poisoning affects on the MnO/Fe(2)O(3) catalyst, especially at lower temperatures.
Subject(s)
Disulfides/chemistry , Ferric Compounds/chemistry , Refuse Disposal/methods , Sulfides/chemistry , Sulfur/chemistry , Catalysis , Incineration , Manganese Compounds/chemistry , Odorants , Oxides/chemistry , VolatilizationABSTRACT
The catalytic incineration of dimethyl sulfide and dimethyl disulfide [(CH3)2S and (CH3)2S2] over an MnO/Fe2O3 catalyst was carried out in a bench-scale catalytic incinerator. Three kinetic models (i.e., the power-rate law, the Mars and Van Krevelen model, and the Langmuir-Hinshelwood model) were used to analyze the results. A differential reactor design was used for best fit of kinetic models in this study. The results show that the Langmuir-Hinshelwood model may be feasible to describe the catalytic incineration of (CH3)2S and (CH3)2S2. This suggests that the chemical adsorption of O2 molecules is important in this incineration.
