Possible involvement of microRNAs in vascular damage in experimental chronic kidney disease

• Published in: Biochimica et biophysica acta Vol. 1842; no. 1; pp. 88 - 98
• Main Authors: Taïbi, Fatiha, Metzinger-Le Meuth, Valérie, M'Baya-Moutoula, Eléonore, Djelouat, Mohamed seif el Islam, Louvet, Loïc, Bugnicourt, Jean-Marc, Poirot, Sabrina, Bengrine, Abderrahmane, Chillon, Jean-Marc, Massy, Ziad A., Metzinger, Laurent
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2014
• Subjects: Animals; Aorta - drug effects; Aorta - metabolism; Aorta - pathology; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - complications; Atherosclerosis - drug therapy; Atherosclerosis - genetics; Atherosclerosis - pathology; Chemokine CXCL12 - genetics; Chemokine CXCL12 - metabolism; Endothelium; Female; Gene Expression Regulation - drug effects; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Kidney disease; Mice; Mice, Knockout; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; NFI Transcription Factors - genetics; NFI Transcription Factors - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Polyamines - pharmacology; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - pathology; Sevelamer; Smooth muscle; Trans-Activators - genetics; Trans-Activators - metabolism; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; Kidney disease; Chol; MYO; Apo-E KO; SDF-1; NFI-A; Smooth muscle; Endothelium; VCAM-1; TG; GLUT-4; Atherosclerosis; miRNA; microRNA; VSMC; CKD; WT; Myocardin; Glucose transporter type 4; Vascular cell adhesion molecule-1; Wild-Type; Chronic kidney disease; Cholesterol; Stromal cell-derived factor-1; Tryglyceride; Nuclear Factor I-A; Vascular smooth muscle cell; Apolipoprotein-E Knock-Out
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2013.10.005

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. •MiR-143 and miR-145 expression is downregulated in CKD and Apo-E KO mice aortas.•MiR-223 and miR-126 expression increases in CKD and Apo-E KO mice aortas.•Sevelamer treatment reverses partially the alteration of microRNA expression.•miRNA alterations were found in serum, indicating a use as noninvasive biomarkers.