MicroRNA-590 Inhibits Lipoprotein Lipase Expression and Prevents Atherosclerosis in apoE Knockout Mice

• Published in: PloS one Vol. 10; no. 9; p. e0138788
• Main Authors: He, Ping-Ping, OuYang, Xin-Ping, Li, Yuan, Lv, Yun-Cheng, Wang, Zong-Bao, Yao, Feng, Xie, Wei, Tan, Yu-Lin, Li, Liang, Zhang, Min, Lan, Gang, Gong, Duo, Cheng, Hai-Peng, Zhong, Hui-Juan, Liu, Dan, Huang, Chong, Li, Zhao-Xia, Zheng, Xi-Long, Yin, Wei-Dong, Tang, Chao-Ke
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.09.2015; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Anniversaries; Aorta; Aorta - enzymology; Aorta - pathology; Apolipoprotein E; Apolipoproteins E - genetics; Arteriosclerosis; Atherosclerosis; Atherosclerosis - enzymology; Cardiovascular disease; Cardiovascular diseases; CD36 antigen; CD36 Antigens - metabolism; Chromatography; Cytokines; Cytokines - blood; Enzyme Repression; Enzyme-linked immunosorbent assay; Gene expression; Genetic aspects; High performance liquid chromatography; Immunofluorescence; Inflammation; Interleukin 6; Lesions; Lipase; Lipid Metabolism; Lipoprotein lipase; Lipoprotein Lipase - genetics; Lipoprotein Lipase - metabolism; Liquid chromatography; Macrophages; Macrophages, Peritoneal - enzymology; Male; Mice; Mice, Knockout; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Monocyte chemoattractant protein 1; mRNA; Physiological aspects; Plasma levels; Prevention; Ribonucleic acid; RNA; RNA Interference; Rodents; Scavenger receptor A1; Scavenger receptors; Tumor necrosis factor-α; Western blotting; Canada; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138788

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 (HPLC)analysis 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-1β)and 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.