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: 5.81). 05/2009; 83(1):131-9. DOI: 10.1093/cvr/cvp121
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atherosclerosis is a typical complex multi-factorial disease and many molecules at different levels and pathways were involved in its development. Some studies have investigated the dysregulation in atherosclerosis at mRNA, miRNA or DNA methylation level, respectively. However, to our knowledge, the studies that integrated these data and revealed the abnormal networks of atherosclerosis have not been reported. Using microarray technology, we analyzed the omics data in atherosclerosis at mRNA, miRNA and DNA methylation levels. Our results demonstrated that the global DNA methylation and expression of miRNA/mRNA were significantly decreased in atherosclerotic plaque than in normal vascular tissue. The interaction network constructed using the integrative data revealed many genes, cellular processes and signaling pathways which were widely considered to play crucial roles in atherosclerosis and also revealed some genes, miRNAs or signaling pathways which have not been investigated in atherosclerosis until now (e.g. miR-519d and SNTB2). Moreover, the overall protein ubiquitination in atherosclerotic plaque was significantly increased. The proteasome activity was increased early but decreased in advanced atherosclerosis. Our study revealed many classic and novel genes and miRNAs involved in atherosclerosis and indicated the effects of ubiquitin-proteasome system on atherosclerosis might be closely related to the course of atherosclerosis. However, the efficacy of proteasome inhibitors in the treatment of atherosclerosis still needs more research.
    PLoS ONE 10/2014; 9(10):e110288. · 3.53 Impact Factor
  • Frontiers in Bioscience 01/2011; 16(1):3133. · 4.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Coronary artery disease (CAD) and pulmonary arterial hypertension (PAH) are two of the most dangerous vascular diseases. Their etiology and pathogenesis are not yet fully understood, thus it remains difficult to achive great advance in the diagnose, therapy and prognosis techniques. microRNAs (miRNAs), a class of highly conserved, small, noncoding RNAs, critically mediate the post-transcriptional gene modulation, which regulates an array of important physiopathological processes including those occurring in cardiac and pulmonary systems. Thereby manipulation of miRNA expression could potentially be applied therapeutically. In this review, we summarize the current knowledge on the roles of miRNAs in the development of vascular diseases, especially in CAD and PAH, providing a theoretical basis for potential uses of miRNA in diagnosis, prognosis, and therapy in these cardiovascular diseases.
    Biocontrol Science and Technology 09/2014; 69(9):643-7. · 0.73 Impact Factor


Available from