title: MicroRNA-590 Inhibits Lipoprotein Lipase Expression and Prevents Atherosclerosis in apoE Knockout Mice.
abstract: 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.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China; Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China; Nursing School, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: He
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China; Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China; Department of Physiology, The Neuroscience Institute, Medical College, University of South China,Hengyang, Hunan, 421001, China.
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: OuYang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.affiliation: Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China; Pharmacy and Biological Science College, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Zong-Bao
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Tan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Gong
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Cheng
authors.affiliation: Department of Cardiovascular Medicine, The Liwan Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510170, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Zhong
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Nursing School, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China; Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China; Pharmacy and Biological Science College, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yin
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerologyof Hunan Province,Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan 421001, China; Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, 28 West Changsheng Road, Hengyang 421001, Hunan, China.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000201:enzymology*; D018955:CD36 Antigens / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004794:Enzyme Repression; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000201:enzymology; D008297:Male; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D016207:Cytokines; C000602617:MIRN590 microRNA, mouse; D035683:MicroRNAs; D008071:Lipoprotein Lipase