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  • Title: Chronic LPSF/GQ-02 treatment attenuates inflammation and atherosclerosis development in LDLr-/- mice.
    Author: Silva AKSE, Gomes FODS, Santos Silva BD, Ribeiro EL, Oliveira AC, Araújo SMDR, de Lima IT, Oliveira AGV, Rudnicki M, Abdalla DSP, Lima MDCA, Pitta IDR, Peixoto CA.
    Journal: Eur J Pharmacol; 2016 Nov 15; 791():622-631. PubMed ID: 27693798.
    Abstract:
    BACKGROUND: Atherosclerosis is a complex disorder with a multifactorial pathogenesis. We previously indicated that the new TZD LPSF/GQ-02 inhibits hepatic steatosis and inflammation, which are reported as risk factors for atherosclerosis development. Here, we explored the effects of LPSF/GQ-02 on atherosclerosis in LDLr-/- mice comparing two treatment periods. METHODS AND RESULTS: LDLr-/- mice were fed a high-fat diet for 10 and 12 weeks and received oral treatment with LPSF/GQ-02 (30mg/kg/day) or pioglitazone (20mg/kg/day) for 15 and 30 days, respectively. Both treatment protocols with LPSF/GQ-02 resulted in lower collagen density in the atherosclerotic lesions. In addition, the treatment for 15 days also decreased mRNA levels of CD40, MCP-1, ABCG1 and upregulated PPARα, whereas the 30-days treatment reduced the protein levels of LOX-1, p-IκBα and p-NFκB. CONCLUSION: This study provides evidence that LPSF/GQ-02 affects the composition and growth of atherosclerotic lesions in LDLr-/- mice. Moreover, our data also support previous findings showing anti-inflammatory properties of LPSF/GQ-02 and reinforce the therapeutic potential of this TZD for treating atherosclerosis and inflammation-related disorders.
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