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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Taibi, Fatiha¹  Metzinger-Le Meuth, Valerie^1,2  M'Baya-Moutoula, Eleonore¹  Djelouat, Mohamed Seif el Islam¹  Louvet, Loic¹  Bugnicourt, Jean-Marc^1,3  Poirot, Sabrina¹  Bengrine, Abderrahmane¹  Chillon, Jean-Marc¹  Massy, Ziad A.^1,4  Metzinger, Laurent^1,5 

[1] Univ Picardie Jules Verne, INSERM, U1088, F-80037 Amiens, France

[2] Univ Paris 13, Sorbonne Paris Cite, UFR SMBH, F-93017 Bobigny, France

[3] Amiens Univ Hosp, Serv Neurol, F-80054 Amiens, France

[4] Paris UVSQ Univ, Ambroise Pare Hosp, Div Nephrol, F-92100 Boulogne Billancourt, France

[5] Amiens Univ Hosp, CBH, F-80054 Amiens, France

关键词: Atherosclerosis;    Endothelium;    Kidney disease;    microRNA;    Smooth muscle;   

DOI  :  10.1016/j.bbadis.2013.10.005

来源: Elsevier

【 摘 要 】

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 musclespecific 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 5DF-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. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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