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

He PP, OuYang XP, Li Y, Lv YC, Wang ZB, Yao F, Xie W, Tan YL, Li L, Zhang M, Lan G, Gong D, Cheng HP, Zhong HJ, Liu D, Huang C, Li ZX, Zheng XL, Yin WD, Tang CK - PLoS ONE (2015)

Bottom Line: Consistently, miR-590 decreased the expression of CD36 and scavenger receptor A1 (SRA1) mRNA and protein.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of miR-590 on SRA1 and CD36 expression in apoE−/− mice.(A) SRA1 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (B) CD36 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (C) SRA1 and CD36 protein levels in peritoneal macrophages of apoE−/− mice as measured by western blotting. Values are mean ± SD.*: P<0.05 vs AG-NC. #: P<0.05 vs AN-NC.
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pone.0138788.g006: Effects of miR-590 on SRA1 and CD36 expression in apoE−/− mice.(A) SRA1 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (B) CD36 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (C) SRA1 and CD36 protein levels in peritoneal macrophages of apoE−/− mice as measured by western blotting. Values are mean ± SD.*: P<0.05 vs AG-NC. #: P<0.05 vs AN-NC.

Mentions: It was previously reported that macrophage LPL could up-regulate the expression of SR-A or CD36, two principal receptors responsible for the uptake of modified LDL in macrophages[24, 25].Therefore we determined the effect of miR-590 on SRA1 and CD36 expression in macrophages from abdominal cavities of apoE−/− mice. As expected, the expression of both SRA1 and CD36 mRNA and protein was reduced in mice treated with miR-590 agomir, but increased in mice treated with miR-590 antagomir (Fig 6A, 6B and 6C), when compared with their respective control group. These findings suggested that miR-590 reduces SRA1 and CD36 expression via suppressing LPL levels.


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

He PP, OuYang XP, Li Y, Lv YC, Wang ZB, Yao F, Xie W, Tan YL, Li L, Zhang M, Lan G, Gong D, Cheng HP, Zhong HJ, Liu D, Huang C, Li ZX, Zheng XL, Yin WD, Tang CK - PLoS ONE (2015)

Effects of miR-590 on SRA1 and CD36 expression in apoE−/− mice.(A) SRA1 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (B) CD36 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (C) SRA1 and CD36 protein levels in peritoneal macrophages of apoE−/− mice as measured by western blotting. Values are mean ± SD.*: P<0.05 vs AG-NC. #: P<0.05 vs AN-NC.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4580638&req=5

pone.0138788.g006: Effects of miR-590 on SRA1 and CD36 expression in apoE−/− mice.(A) SRA1 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (B) CD36 mRNA levels in peritoneal macrophages of apoE−/− mice as measured by RT-qPCR. (C) SRA1 and CD36 protein levels in peritoneal macrophages of apoE−/− mice as measured by western blotting. Values are mean ± SD.*: P<0.05 vs AG-NC. #: P<0.05 vs AN-NC.
Mentions: It was previously reported that macrophage LPL could up-regulate the expression of SR-A or CD36, two principal receptors responsible for the uptake of modified LDL in macrophages[24, 25].Therefore we determined the effect of miR-590 on SRA1 and CD36 expression in macrophages from abdominal cavities of apoE−/− mice. As expected, the expression of both SRA1 and CD36 mRNA and protein was reduced in mice treated with miR-590 agomir, but increased in mice treated with miR-590 antagomir (Fig 6A, 6B and 6C), when compared with their respective control group. These findings suggested that miR-590 reduces SRA1 and CD36 expression via suppressing LPL levels.

Bottom Line: Consistently, miR-590 decreased the expression of CD36 and scavenger receptor A1 (SRA1) mRNA and protein.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus