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http://purl.uniprot.org/citations/24675724http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24675724http://www.w3.org/2000/01/rdf-schema#comment"

Aim

MicroRNAs (miRNAs) play key roles in inflammatory responses of macrophages. However, the function of miRNAs in macrophage-derived foam cell formation is unclear. Here, we investigated the role of miRNAs in macrophage-derived foam cell formation and atherosclerotic development.

Methods and results

Using quantitative reverse transcription-PCR (qRT-PCR), we found that the level of miR-155 expression was increased significantly in both plasma and macrophages from atherosclerosis (ApoE(-/-)) mice. We identified that oxidized low density lipoprotein (oxLDL) induced the expression and release of miR-155 in macrophages, and that miR-155 was required to mediate oxLDL-induced lipid uptake and reactive oxygen species (ROS) production of macrophages. Furthermore, ectopic overexpression and knockdown experiments identified that HMG box-transcription protein1 (HBP1) is a novel target of miR-155. Knockdown of HBP1 enhanced lipid uptake and ROS production in oxLDL-stimulated macrophages, and overexpression of HBP1 repressed these effects. Furthermore, bioinformatics analysis identified three YY1 binding sites in the promoter region of pri-miR-155 and verified YY1 binding directly to its promoter region. Detailed analysis showed that the YY1/HDAC2/4 complex negatively regulated the expression of miR-155 to suppress oxLDL-induced foam cell formation. Importantly, inhibition of miR-155 by a systemically delivered antagomiR-155 decreased clearly lipid-loading in macrophages and reduced atherosclerotic plaques in ApoE(-/-) mice. Moreover, we observed that the level of miR-155 expression was up-regulated in CD14(+) monocytes from patients with coronary heart disease.

Conclusion

Our findings reveal a new regulatory pathway of YY1/HDACs/miR-155/HBP1 in macrophage-derived foam cell formation during early atherogenesis and suggest that miR-155 is a potential therapeutic target for atherosclerosis."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.org/dc/terms/identifier"doi:10.1093/cvr/cvu070"xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Huang S."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Li Q."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Zou J."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Zhang Y.Y."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Shen N."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Jing Q."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Qin Y.W."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Zeng A."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Wang G.K."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Yang H.T."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Zhao X.X."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Zhu J.Q."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Han X.S."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Tian F.J."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"Zhu R.F."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/author"An L.N."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/name"Cardiovasc Res"xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/pages"100-110"xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/title"Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in atherogenesis."xsd:string
http://purl.uniprot.org/citations/24675724http://purl.uniprot.org/core/volume"103"xsd:string
http://purl.uniprot.org/citations/24675724http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24675724
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