title: MicroRNA-125a-5p alleviates the deleterious effects of ox-LDL on multiple functions of human brain microvessel endothelial cells.
abstract: MicroRNA-125a-5p (miR-125a-5p) could participate in the pathogenesis of vascular diseases. In this study, we investigated the role of miR-125a-5p in oxidized low-density lipoprotein (ox-LDL)-induced functional changes in human brain microvessel endothelial cells (HBMEC). The reactive oxygen species (ROS) production, nitric oxide (NO) generation, senescence, apoptosis, and functions of HBMEC were analyzed. For mechanism study, the epidermal growth factor receptor (EGFR)/extracellular signal-regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway and phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase (Akt)/endothelial nitric oxide synthase (eNOS) pathway were analyzed. Results showed the following:1) Expression of miR-125a-5p was reduced in ox-LDL-treated HBMEC.2) Overexpression of miR-125a-5p protected HBMEC from ox-LDL-induced apoptosis, senescence, ROS production, and NO reduction.3) Overexpression of miR-125a-5p increased HBMEC proliferation, migration, and tube formation, while decreasing HBMEC adhesion to leukocytes, as well as counteracting the effects of ox-LDL on those functions.4) The levels of EGFR/ERK/p38 MAPK pathway, PI3K/Akt/eNOS pathway, cleaved caspase-3, and adherent molecular ICAM-1 and VCAM-1 were associated with the effects of ox-LDL on these HBMEC functions. In conclusion, miR-125a-5p could counteract the effects of ox-LDL on various HBMEC functions via regulating the EGFR/ERK/p38 MAPK and PI3K/Akt/eNOS pathways and cleaved caspase-3, ICAM-1, and VCAM-1 expression.
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
authors.forename: Qunwen
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Liao
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.|Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio; and.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Eric
authors.initials: E
authors.lastname: Lazartigues
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China; mxtgdmc@163.com.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000166:cytology / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D035683:MicroRNAs / Q000378:metabolism*; D055806:Microvessels / Q000166:cytology / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases
keywords: cell function; human brain microvessel endothelial cells; miR-125a-5p; oxidized low-density lipoprotein; signal pathway