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9th Edition of Global Conference on

Pharmaceutics and Novel Drug Delivery Systems

June 12-13, 2023 | Rome, Italy

PHARMACEUTICS 2022

Non-coding RNAs in the cardiovascular disorders linked to Chronic Kidney Disease

Speaker at Pharmaceutics and Novel Drug Delivery Systems 2022 - Laurent Metzinger
University of Picardie Jules Verne, France
Title : Non-coding RNAs in the cardiovascular disorders linked to Chronic Kidney Disease

Abstract:

Non-coding RNAs were discovered at the turn of the 21th century. Several families exist, including long non-coding RNAs, and short non -coding RNAs. The importance of these various RNA species are just beginning to be understood in the nephrology field, and related cardiovascular diseases.  MicroRNAs (miRNAs) are involved in the post-transcriptional regulation by modulating expression of several messenger RNAs. Up to 3 000 miRNAs are expressed by human cells. They are 21-25 nt single stranded nucleic acids that trigger translational repression of mRNA by base pairing with the 3' untranslated region of up to a hundred mRNA targets. Renal diseases are consecutive to a deregulation of gene expression, which is at least in part modulated by non-coding RNAs. We and others have shown in the last 12 years that several miRNAs are deregulated during the onset of Chronic kidney disease (CKD) which is linked with cardiovascular damages. miR-223 expression is increased in vivo in big vessels of a mouse model of CKD whereas it is decreased in the serum of both murine models but also human CKD patients. Results on a cohort of 627 CKD patients will be shown.

We also evaluated the impact of miR-223 modulation on restenosis in a rat model of carotid artery after balloon injury. The up- and down-expression of miR-223 were induced by adenoviral vectors, that coded either a pre-miR-223 sequence allowing artificial miR-223 over-expression or a sponge sequence, to trapp and inhibit the endogenous miRNA respectively. Restenosis was measured on stained rat carotid sections. We showed that down-expression of miR-223 significantly reduced neointimal hyperplasia in carotids, and was correlated with a 2-3-fold overexpression of miR-223 targets in vitro. We concluded that the down-regulation miR-223 by a sponge strategy may protect against restenosis and could be an innovative therapeutic approach in order to protect blood vessels from restenosis after angioplasty.

Biography:

Laurent Metzinger has completed his PhD in Biological Sciences and Pharmaceutical studies in Strasbourg, France and was a postdoctoral fellow from the University of Oxford (UK) in a leading lab on Duchenne muscular Dystrophy (Pr. Kay Davies). He works on microRNA regulation in the HEMATIM team in Amiens, and focuses on anemia and related vascular disorders associated with Chronic Kidney DIsease. He has authored some of the first papers showing a role for microRNAs in CKD and published in reputed journals, including Nature and Cell. He teaches Biochemistry, Genetics and Molecular Biology in the Pharmacy School of Amiens (Université de Picardie Jules Verne).

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