title: MicroRNA-29b promotes high-fat diet-stimulated endothelial permeability and apoptosis in apoE knock-out mice by down-regulating MT1 expression.
abstract: BACKGROUND
  High-fat diet has been reported to be associated with cardiovascular diseases which is implicated in atherosclerosis. However, the underlying mechanisms remain unknown. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to be involved in atherosclerosis.
  
  
  RESULTS
  This study examined whether microRNA-29b (miR-29b) regulates high-fat diet induced endothelial permeability and apoptosis by targeting MT1, a known melatonin membrane receptor. In apoE knock-out mice, a high-fat diet increased miR-29b expression and induced apoptosis as determined by up-regulation of caspase-3 activity. However, a standard diet did not alter apoptosis. miR-29b antagomir decreased endothelial permeability and apoptosis in high-fat diet-stimulated mice. In contrast, a miR-29b mimic enhanced endothelial permeability and apoptosis. The induction of miR-29b correlated with a reduction in Bcl-2 and MT1 in high-fat diet-stimulated mice. miR-29b have an effect on the marker of inflammation (NF-κB) and cell adhesion molecule (ICAM-1). We further showed that miR-29b targeted and inhibited MT1 expression through a target site located in the 3'un-translational region of MT1 mRNA. This study demonstrates a role of miR-29b in atherosclerosis and identifies MT1 as a direct target of miR-29b.
  
  
  CONCLUSIONS
  The effect of miR-29b on endothelial permeability and apoptosis is mediated through the down-regulation of MT1. Thus, miR-29b may be a new therapeutic target for atherosclerosis.
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, People's Republic of China; Key Laboratory of Gene Research of Anhui Province, Hefei, Anhui, People's Republic of China. Electronic address: aydzhq@126.com.
authors.forename: Hua-Qing
authors.initials: HQ
authors.lastname: Zhu
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, People's Republic of China; Key Laboratory of Gene Research of Anhui Province, Hefei, Anhui, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: li
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, Anhui, People's Republic of China.
authors.forename: Liu-Yi
authors.initials: LY
authors.lastname: Dong
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, People's Republic of China; Key Laboratory of Gene Research of Anhui Province, Hefei, Anhui, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Oncology, The first Affiliated Hospital of Anhui Medical University, Anhui, People's Republic of China. Electronic address: wanghua@ahmu.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, People's Republic of China; Key Laboratory of Gene Research of Anhui Province, Hefei, Anhui, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D017209:Apoptosis / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D015536:Down-Regulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis*; D011897:Random Allocation; D044122:Receptor, Melatonin, MT1 / Q000096:biosynthesis*
chemical_list: D001057:Apolipoproteins E; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D044122:Receptor, Melatonin, MT1
keywords: Apoptosis; High-fat diet; MT1; MicroRNA-29b; Permeability