|Title:||Rosiglitazone but not losartan prevents Nrf-2 dependent CD36 gene expression up-regulation in an in vivo atherosclerosis model||Authors:||Hernandez-Trujillo, Y.
Rodriguez-Perez, Jose C.
Ppar-Gamma, et al
|Issue Date:||2008||Journal:||Cardiovascular Diabetology||Abstract:||Background: Thiazolidinediones exert anti-inflammatory and anti-oxidative roles and attenuate atherosclerosis by mechanisms partially independent of their metabolizing actions. High doses of angiotensin type I receptor (AT(1)R) blocker losartan (LST) seem to promote fat cell formation by preserving PPAR gamma activity.Methods: C57BL/ 6J diet-induced atherosclerotic susceptible mice randomly received a normal or a high-fat high-cholesterol (HFHC) diet and were treated with rosiglitazone (RG), LST or a vehicle for 12 weeks.Results: HFHC was associated with increased PPAR gamma gene expression without an over regulation of PPAR. responsive genes, whereas RG and LST treatments were found to maintain PPAR gamma activity without resulting in increased PPAR gamma gene expression. A better anti-inflammatory and antioxidant profile in mice treated with RG regarding LST was observed in spite of a similar PPAR gamma preserved activity. Chromatin immunoprecipitation (ChIP) assays revealed that animals under HFHC diet treated with RG showed a significant nuclear factor erythroid 2-like 2 (Nrf2)-dependent down-regulation of the expression of the CD36 gene.Conclusion: The PPAR gamma agonist RG exerts antioxidant properties that significantly reduced Nrf2-dependent CD-36 up-regulation in mice under HFHC diet. Because LST treatment was also associated with a preserved PPAR gamma activity, our data suggests that these RG antioxidant effects are partially independent of its PPAR gamma metabolizing properties.||URI:||http://hdl.handle.net/10553/49324||ISSN:||1475-2840||DOI:||10.1186/1475-2840-7-3||Source:||Cardiovascular diabetology,v. 7, p. 3|
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