MicroRNA-590 Inhibits Lipoprotein Lipase Expression and Prevents Atherosclerosis in apoE Knockout MiceReportar como inadecuado

MicroRNA-590 Inhibits Lipoprotein Lipase Expression and Prevents Atherosclerosis in apoE Knockout Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Recent studies have suggested that miR-590 may play critical roles in cardiovascular disease. This study was designed to determine the effects of miR-590 on lipoprotein lipase LPL expression and development of atherosclerosis in apolipoprotein E knockout apoE−-− mice and explore the potential mechanisms. En face analysis of the whole aorta revealed that miR-590 significantly decreased aortic atherosclerotic plaque size and lipid content in apoE−-− mice. Double immunofluorescence staining in cross-sections of the proximal aorta showed that miR-590 agomir reduced CD68 and LPL expression in macrophages in atherosclerotic lesions. MiR-590 agomir down-regulated LPL mRNA and protein expression as analyzed by RT-qPCR and western blotting analyses, respectively. Consistently, miR-590 decreased the expression of CD36 and scavenger receptor A1 SRA1 mRNA and protein. High-performance liquid chromatography HPLCanalysis confirmed that treatment with miR-590 agomir reduced lipid levels either in plasma orinabdominal cavity macrophages of apoE−-− mice. ELISA analysis showed that miR-590 agomir decreased plasma levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha TNF-α, monocyte chemotactic protein-1 MCP-1, interleukin-1β IL-1βand interleukin-6 IL-6. In contrast, treatment with miR-590 antagomir prevented or reversed these effects. Taken together, these results reveal a novel mechanism of miR-590 effects, and may provide new insights into the development of strategies for attenuating lipid accumulation and pro-inflammatory cytokine secretion.

Autor: Ping-Ping He , Xin-Ping OuYang , Yuan Li , Yun-Cheng Lv, Zong-Bao Wang, Feng Yao, Wei Xie, Yu-Lin Tan, Liang Li, Min Zhang, Gang

Fuente: http://plos.srce.hr/


Documentos relacionados