Chronic LPSF/GQ-02 treatment attenuates inflammation and atherosclerosis development in LDLr^−/− mice

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• 作者：Amanda Karolina Soares e Silva^a ; ^b ; Fabiana Oliveira dos Santos Gomes^a ; ^b ; Bruna dos Santos Silva^a ; ^b ; Edlene Lima Ribeiro^a ; ^b ; Amanda Costa Oliveira^a ; ^b ; Shyrlene Meyre da Rocha Araú ; jo^a ; ^b ; Ingrid Tavares de Lima^a ; ^b ; Anne Gabrielle Vasconcelos Oliveira^c ; Martina Rudnicki^d ; Dulcineia S.P. Abdalla^d ; Maria do Carmo Alves de Lima^e ; Ivan da Rocha Pitta^e ; Christina Alves Peixoto^a ; ^{peixoto.christina@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Atherosclerosis ; Inflammation ; LPSF/GQ-02 ; Thiazolidinediones
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：791
• 期：Complete
• 页码：622-631
• 全文大小：1355 K

文摘

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.

bsSec_2">Methods and results

LDLr^−/− mice were fed a high-fat diet for 10 and 12 weeks and received oral treatment with LPSF/GQ-02 (30 mg/kg/day) or pioglitazone (20 mg/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.

bsSec_3">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.