title: miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress.
abstract: Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study focused on the effect of laminar shear stress (LSS) on human endothelial cells (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECs in vitro to LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4 (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression.
authors.affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France ; INSERM U1148, LVTS, UFR SMBH, University Paris 13 Sorbonne Paris Cité, 74 rue Marcel Cachin, 93000 Bobigny, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Mondadori dos Santos
authors.affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France ; Centre de Biologie Humaine (CBH), Amiens University Hospital, 80054 Amiens, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Metzinger
authors.affiliation: INSERM U1148, LVTS, UFR SMBH, University Paris 13 Sorbonne Paris Cité, 74 rue Marcel Cachin, 93000 Bobigny, France.
authors.forename: Oualid
authors.initials: O
authors.lastname: Haddad
authors.affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France.
authors.forename: Eléonore
authors.initials: E
authors.lastname: M'baya-Moutoula
authors.affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Taïbi
authors.affiliation: INSERM U1148, LVTS, UFR SMBH, University Paris 13 Sorbonne Paris Cité, 74 rue Marcel Cachin, 93000 Bobigny, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Charnaux
authors.affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France ; Division of Nephrology, Ambroise Pare Hospital, Paris Ile de France Ouest (UVSQ) University, 09 avenue Charles de Gaulle, 92100 Boulogne Billancourt Cedex, France.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.affiliation: INSERM U1148, LVTS, UFR SMBH, University Paris 13 Sorbonne Paris Cité, 74 rue Marcel Cachin, 93000 Bobigny, France.
authors.forename: Hanna
authors.initials: H
authors.lastname: Hlawaty
authors.affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France ; University Paris 13 Sorbonne Paris Cité, UFR SMBH, 74 rue Marcel Cachin, 93017 Bobigny, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Metzinger-Le Meuth
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D048430:Cell Shape; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D020710:RGS Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D013314:Stress, Mechanical; D053668:Syndecan-1 / Q000378:metabolism; D053671:Syndecan-4 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D066253:Vascular Remodeling / Q000235:genetics*
chemical_list: D000199:Actins; D001057:Apolipoproteins E; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D020710:RGS Proteins; C107413:RGS16 protein; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D053668:Syndecan-1; D053671:Syndecan-4; D019010:Vascular Cell Adhesion Molecule-1