title: Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries.
abstract: Lectin-like low-density lipoprotein receptor 1 (LOX-1) is a receptor for oxidized low density lipoprotein (oxLDL) in endothelial cells. The activation of LOX-1 by oxLDL stimulates the apoptosis and dysfunction of endothelial cells, and contributes to atherogenesis. However, the regulatory factors for LOX-1 are still unclear. MicroRNAs are small, endogenous, non-coding RNAs that regulate gene expressions at a post-transcriptional level. The let-7 family is the second microRNA been discovered, which plays important roles in cardiovascular diseases. Let-7a and let-7b were predicted to target LOX-1 3'-UTR and be highly expressed in endothelial cells. The present study demonstrated that LOX-1 was a target of let-7a and let-7b. They inhibited the expression of LOX-1 by targeting the positions of 310-316 in LOX-1 3'-UTR. Over-expression of let-7a and let-7b inhibited the oxLDL-induced endothelial cell apoptosis, NO deficiency, ROS over-production, LOX-1 upregulation and endothelial nitric oxide synthase (eNOS) downregulation. Moreover, we found that oxLDL treatment induced p38MAPK phosphorylation, NF-κB nuclear translocation, IκB degradation and PKB dephosphorylation. Let-7a or let-7b over-expression attenuated these alterations significantly. The present study may provide a new insight into the protective properties of let-7a and let-7b in preventing the endothelial dysfunction associated with cardiovascular disease, such as atherosclerosis.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, China; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Bao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Lou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001665:Binding Sites; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; C487931:mirnlet7 microRNA, human; C099252:oxidized low density lipoprotein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III