Ping-Ping He1, Xin-Ping Ouyang2, Yan-Yan Tang3, Li Liao4, Zong-Bao Wang5, Yun-Cheng Lv3, Guo-Ping Tian6, Guo-Jun Zhao3, Liang Huang3, Feng Yao3, Wei Xie3, Yu Lin Tang3, Wu-Jun Chen3, Min Zhang3, Yuan Li3, Jian-Feng Wu3, Juan Peng3, Xiang-Yu Liu3, Xi-Long Zheng7, Wei-Dong Yin8, Chao-Ke Tang9. 1. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; School of Nursing, University of South China, Hengyang, Hunan 421001, China. 2. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; Department of Physiology, The Neuroscience Institute, Medical College, University of South China, Hengyang, Hunan 421001, China. 3. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China. 4. School of Nursing, University of South China, Hengyang, Hunan 421001, China. 5. Pharmacy and Biological Science College, University of South China, Hengyang, Hunan 421001, China. 6. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China. 7. Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada. 8. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; Pharmacy and Biological Science College, University of South China, Hengyang, Hunan 421001, China. Electronic address: wdy20042004@126.com. 9. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China. Electronic address: tangchaoke@qq.com.
Abstract
BACKGROUND: Accumulating evidence suggests that microRNA-590 (miR-590) has protective effects on cardiovascular diseases, but the mechanism is unknown. Interestingly, previous studies from our laboratory and others have shown that macrophage-derived lipoprotein lipase (LPL) might accelerate atherosclerosis by promoting lipid accumulation and inflammatory response. However, the regulation of LPL at the post-transcriptional level by microRNAs has not been fully understood. In this study, we explored whether miR-590 affects the expression of LPL and its potential subsequent effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. METHODS AND RESULTS: Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-590 directly inhibited LPL protein and mRNA expression by targeting LPL 3'UTR. LPL Activity Assays showed that miR-590 reduced LPL activity in the culture media. Oil Red O staining and high-performance liquid chromatography assays showed that miR-590 had inhibitory effects on the lipid accumulation in human THP-1 macrophages. We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. With the method of small interfering RNA, we found that LPL siRNA can inhibit the miR-590 inhibitor-induced increase in lipid accumulation and secretion of pro-inflammatory cytokines in oxLDL-treated human THP-1 macrophages. CONCLUSIONS: MiR-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting LPL gene in human THP-1 macrophages. Therefore, targeting miR-590 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.
BACKGROUND: Accumulating evidence suggests that microRNA-590 (miR-590) has protective effects on cardiovascular diseases, but the mechanism is unknown. Interestingly, previous studies from our laboratory and others have shown that macrophage-derived lipoprotein lipase (LPL) might accelerate atherosclerosis by promoting lipid accumulation and inflammatory response. However, the regulation of LPL at the post-transcriptional level by microRNAs has not been fully understood. In this study, we explored whether miR-590 affects the expression of LPL and its potential subsequent effects on lipid accumulation and pro-inflammatory cytokine secretion in humanTHP-1 macrophages. METHODS AND RESULTS: Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-590 directly inhibited LPL protein and mRNA expression by targeting LPL 3'UTR. LPL Activity Assays showed that miR-590 reduced LPL activity in the culture media. Oil Red O staining and high-performance liquid chromatography assays showed that miR-590 had inhibitory effects on the lipid accumulation in humanTHP-1 macrophages. We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in humanTHP-1 macrophages as measured by ELISA. With the method of small interfering RNA, we found that LPL siRNA can inhibit the miR-590 inhibitor-induced increase in lipid accumulation and secretion of pro-inflammatory cytokines in oxLDL-treated humanTHP-1 macrophages. CONCLUSIONS:MiR-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting LPL gene in humanTHP-1 macrophages. Therefore, targeting miR-590 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.
Authors: Dimitry A Chistiakov; Alexandra A Melnichenko; Veronika A Myasoedova; Andrey V Grechko; Alexander N Orekhov Journal: J Mol Med (Berl) Date: 2017-08-07 Impact factor: 4.599
Authors: Dong Ju Son; Yu Yeon Jung; Young Sik Seo; Heonyong Park; Dong Hun Lee; Sanghyeon Kim; Yoon-Seok Roh; Sang Bae Han; Do Young Yoon; Jin Tae Hong Journal: Theranostics Date: 2017-06-01 Impact factor: 11.556