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The effects of miR-467b on lipoprotein lipase (LPL) expression, pro-inflammatory cytokine, lipid levels and atherosclerotic lesions in apolipoprotein E knockout mice

Author:
Tian, Guo-Ping, Tang, Yan-Yan, He, Ping-Ping, Lv, Yun-Cheng, Ouyang, Xin-Pin, Zhao, Guo-Jun, Tang, Shi-Lin, Wu, Jian-Feng, Wang, Jia-Lin, Peng, Juan, Zhang, Min, Li, Yuan, Cayabyab, Francisco S., Zheng, Xi-Long, Zhang, Da-Wei, Yin, Wei-Dong, Tang, Chao-Ke
Source:
Biochemical and biophysical research communications 2014 v.443 pp. 428-434
ISSN:
0006-291X
Subject:
Western blotting, abdominal cavity, aorta, apolipoprotein E, atherosclerosis, blood plasma, chemokine CCL2, gene expression, gene expression regulation, genes, high density lipoprotein cholesterol, inflammation, interleukin-1beta, interleukin-6, knockout mutants, lipid metabolism, lipoprotein lipase, low density lipoprotein cholesterol, macrophages, mice, microRNA, quantitative polymerase chain reaction, secretion, triacylglycerols, tumor necrosis factor-alpha
Abstract:
Atherosclerosis is a lipid disorder disease characterized by chronic blood vessel wall inflammation driven by the subendothelial accumulation of macrophages. Studies have shown that lipoprotein lipase (LPL) participates in lipid metabolism, but it is not yet known whether post-transcriptional regulation of LPL gene expression by microRNAs (miRNAs) occurs in vivo. Here, we tested that miR-467b provides protection against atherosclerosis by regulating the target gene LPL which leads to reductions in LPL expression, lipid accumulation, progression of atherosclerosis and production of inflammatory cytokines in apolipoprotein E knockout (apoE−/−) mice. Treatment of apoE−/− mice with intra-peritoneal injection of miR-467b agomir led to decreased blood plasma levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β and monocyte chemotactic protein-1 (MCP-1). Using Western blots and real time PCR, we determined that LPL expression in aorta and abdominal cavity macrophages were significantly down-regulated in the miR-467b agomir group. Furthermore, systemic treatment with miR-467b antagomir accelerated the progression of atherosclerosis in the aorta of apoE−/− mice. The present study showed that miR-467b protects apoE−/− mice from atherosclerosis by reducing lipid accumulation and inflammatory cytokine secretion via downregulation of LPL expression. Therefore, targeting miR-467b may offer a promising strategy to treat atherosclerotic vascular disease.
Agid:
5329300