title: Possible involvement of microRNAs in vascular damage in experimental chronic kidney disease.
abstract: Chronic kidney disease (CKD) is associated with vascular calcifications and atherosclerosis. There is a need for novel predictors to allow earlier diagnosis of these disorders, predict disease progression, and improve assessment of treatment response. We focused on microRNAs since they are implicated in a variety of cellular functions in cardiovascular pathology. We examined changes of microRNA expression in aortas of CKD and non-CKD wild type mice and apolipoprotein E knock-out mice, respectively. Both vascular smooth muscle-specific miR-143 and miR-145 expressions were decreased in states of atherosclerosis and/or CKD or both, and the expression level of protein target Myocardin was increased. The inflammatory miR-223 was increased in more advanced stages of CKD, and specific protein targets NFI-A and GLUT-4 were dramatically decreased. Expression of miR-126 was markedly increased and expression of protein targets VCAM-1 and SDF-1 was altered during the course of CKD. The drug sevelamer, commonly used in CKD, corrected partially these changes in microRNA expression, suggesting a direct link between the observed microRNA alterations and uremic vascular toxicity. Finally, miR-126, -143 and -223 expression levels were deregulated in murine serum during the course of experimental CKD. In conclusion, these miRNAs could have role(s) in CKD vascular remodeling and may therefore represent useful targets to prevent or treat complications of CKD.
authors.affiliation: INSERM U1088, 1 Rue des Louvels, F-80037 Amiens, University of Picardie Jules Verne, Amiens, France.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Taïbi
authors.forename: Valérie
authors.initials: V
authors.lastname: Metzinger-Le Meuth
authors.forename: Eléonore
authors.initials: E
authors.lastname: M'Baya-Moutoula
authors.forename: Mohamed seif el Islam
authors.initials: Ms
authors.lastname: Djelouat
authors.forename: Loïc
authors.initials: L
authors.lastname: Louvet
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Bugnicourt
authors.forename: Sabrina
authors.initials: S
authors.lastname: Poirot
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Bengrine
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Chillon
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.forename: Laurent
authors.initials: L
authors.lastname: Metzinger
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000069603:Sevelamer; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D000099251:Myocardin
chemical_list: D001057:Apolipoproteins E; D054377:Chemokine CXCL12; D051275:Glucose Transporter Type 4; D035683:MicroRNAs; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011073:Polyamines; D000069603:Sevelamer; D015534:Trans-Activators; D019010:Vascular Cell Adhesion Molecule-1; D000099251:Myocardin; C515256:Cxcl12 protein, mouse; C545201:MIRN126 microRNA, mouse; C543499:MIRN145a microRNA, mouse; C544877:MIRN223 microRNA, mouse; C532884:MIRN143 microRNA, mouse; C497646:Nfia protein, mouse; C495693:Slc2a4 protein, mouse
keywords: Apo-E KO; Apolipoprotein-E Knock-Out; Atherosclerosis; CKD; Chol; Cholesterol; Chronic kidney disease; Endothelium; GLUT-4; Glucose transporter type 4; Kidney disease; MYO; Myocardin; NFI-A; Nuclear Factor I-A; SDF-1; Smooth muscle; Stromal cell-derived factor-1; TG; Tryglyceride; VCAM-1; VSMC; Vascular cell adhesion molecule-1; Vascular smooth muscle cell; WT; Wild-Type; miRNA; microRNA