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| Título: | New indole-thiazolidine attenuates atherosclerosis in LDLr-/- mice |
Autor: | César, Fernanda A.; Heras, Beatriz de las; Boscá, Lisardo CSIC ORCID CVN ; Abdalla, Dulcineia S. P. | Fecha de publicación: | 2015 | Editor: | Elsevier | Citación: | Vascular Pharmacology 71: 174-180 (2015) | Resumen: | Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor γ (PPARγ) agonists that improve insulin-mediated glucose uptake and possess beneficial vasculoprotective actions. However, because undesirable side effects are associated with these drugs, novel TZDs are under development. In this study, we evaluated the biological activity of LYSO-7, a new indole-thiazolidine, on PPAR activation, inflammation and atherogenesis using a gene reporter assay, lipopolysaccharide (LPS)-activated RAW 264.7 cell culture, and a low-density lipoprotein receptor knockout (LDLr−/−) mouse model of atherosclerosis. LYSO-7 shows low cytotoxicity in RAW 264.7 cells and at 2.5 μmol/L induces PPARα and PPARγ transactivation as well as inhibits LPS-induced nitrite production and the mRNA gene expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). In addition, treatment with LYSO-7 reduces the development of atherosclerosis in LDLr−/− mice, improves the lipid profile, blood glucose levels, and downregulates CD40 and CD40L expression without affecting the body weight of the animals. Altogether, our data show that LYSO-7 possesses anti-inflammatory properties and that treatment with this TZD attenuates atherosclerosis progression in LDLr−/− mice by modulating lipid metabolism and inflammation. Thus, LYSO-7 shows potential as a new drug candidate for the treatment of atherosclerosis. | Descripción: | et al. | URI: | http://hdl.handle.net/10261/124778 | DOI: | 10.1016/j.vph.2015.03.009 | Identificadores: | doi: 10.1016/j.vph.2015.03.009 issn: 1537-1891 e-issn: 1879-3649 |
| Aparece en las colecciones: | (IIBM) Artículos |
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