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Cardiovascular Research Advance Access [Accepted Manuscript] published online on April 17, 2009

Cardiovascular Research, doi:10.1093/cvr/cvp121
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

MicroRNA-125a-5p partly regulates the inflammatory response, lipid uptake and ORP9 expression in oxLDL-stimulated monocyte/macrophages

Ting Chen1, Zhouqing Huang1, Liansheng Wang1, Yue Wang1, Feizhen Wu2, Shu Meng1 and Changqian Wang1,*

1 Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, peoples R China
2 Department of Bio-electronic Center, ShangHai University, shanghai, peoples R China

* Address for Correspondence: Changqian Wang, Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 1665 Kongjiang Road, Shanghai 200092, P.R. China. Tel: (+86 21) 33776115. Fax: (+86 21) 65790000-7058 E-mail: ting010151452{at}yahoo.com.cn

Aims: The inflammatory responses of monocytes/macrophages and the stimulation of lipid uptake into these cells by oxidized low density lipoprotein (oxLDL) are critical to the initiation and development of atherosclerosis. Increasing evidence has demonstrated that many microRNAs play important roles in the cell proliferation, apoptosis, and differentiation that accompany inflammatory responses. However, whether microRNAs are associated with monocyte/macrophage inflammatory responses or oxLDL stimulation is not yet known. The aim of the present study is to investigate microRNAs in monocytes/macrophages and their potential role in oxLDL-stimulation of lipid uptake and other atherosclerotic responses.

Methods and results: Microarrays were used to analyze the global expression of microRNAs in oxLDL-stimulated human primary peripheral blood monocytes. Expression profiles of the microRNAs were verified using TaqMan Real-time PCR. Five microRNAs (microRNA-125a-5p, microRNA-9, microRNA-146a, microRNA-146b-5p, and microRNA-155) were aberrantly expressed after oxLDL treatment of human primary monocytes. Bioinformatics analysis suggested that microRNA-125a-5p is related to a protein similar to ORP9 (oxysterol binding protein-like 9) and this was confirmed by a luciferase reporter assay. MicroRNA-125a-5p was found to mediate lipid uptake and to decrease the secretion of some inflammatory cytokines (Interleukin-2, Interleukin-6, tumor necrosis factor-{alpha}, Transforming Growth Factor-beta) in oxLDL-stimulated monocyte-derived macrophages.

Conclusions: MicroRNA-125a-5p may partly provide post-transcriptional regulation of the proinflammatory response, lipid uptake, and expression of ORP9 in oxLDL-stimulated monocyte/macrophages.

KEYWORDS microRNA; oxLDL; monocytes/macrophages; microarray; inflammation


Time for primary review: 26 Days


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