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

Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, Peoples Republic of China.
Cardiovascular Research (Impact Factor: 5.94). 05/2009; 83(1):131-9. DOI: 10.1093/cvr/cvp121
Source: PubMed


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.
Microarrays were used to analyse 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, tumour necrosis factor-alpha, transforming growth factor-beta) in oxLDL-stimulated monocyte-derived macrophages.
MicroRNA-125a-5p may partly provide post-transcriptional regulation of the proinflammatory response, lipid uptake, and expression of ORP9 in oxLDL-stimulated monocyte/macrophages.

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    • "Modulation of vascular inflammation and angiogenesis (Grundmann et al, 2011) miR-125a Modulates capture of oxLDL by macrophages (Chen et al, 2009) miR-127 Modulation of vascular inflammation and oxidative stress (Santovito et al, 2012) miR-133a, miR-145 Regulation of vascular remodeling and inflammation by controlling VSMC proliferation and differentiation (Torella et al, 2011; Cordes et al, 2009) miR-155 Modulation of endothelial dysfunction, macrophages differentiation and lipid uptake in oxLDL (Huang et al, 2010) miR-221 Promotes reendothelialization and neo-angiogenesis (Davis et al, 2009) oxLDL, Oxidized low-density lipoprotein; VSMC, vascular smooth muscle cell. "
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    • "These miRNA include miR-206, miR-145, miR-143 and miR-221, all of which have been shown to regulate vascular smooth muscle cell proliferation, migration and differentiation , affecting vasculature phenotypic building (Cordes et al. 2009; Boettger et al. 2009; Davis et al. 2009; Liu et al. 2009; Cheng and Zhang 2010; Caruso et al. 2012; Jalali et al. 2012). Moreover, miR-204, miR-155, miR-146 and miR-125a-5p regulated the vascular pathological reaction depending on the related mononuclear cells and inflammatory factor (Taganov et al. 2006; Ceppi et al. 2009; Chen et al. 2009; Shen et al. 2010; Courboulin et al. 2011). "
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