Evaluation of anti-fibrotic treatments in renovascular hypertension via targeting long noncoding RNAs

Details

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Version: After imprimatur
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Serval ID
serval:BIB_D08814F4A035
Type
A Master's thesis.
Publication sub-type
Master (thesis) (master)
Collection
Publications
Institution
Title
Evaluation of anti-fibrotic treatments in renovascular hypertension via targeting long noncoding RNAs
Author(s)
GLAIZOT L.
Director(s)
PEDRAZZINI T.
Codirector(s)
AGHAGOLZADEH P.
Institution details
Université de Lausanne, Faculté de biologie et médecine
Publication state
Accepted
Issued date
2021
Language
english
Number of pages
24
Abstract
Since non-coding RNAs have started to be explored and characterized, thousands of long non- coding RNAs (lncRNAs) were investigated for their functions, ways of action, and therapeutic potential. In the process of discovering novel lncRNA with function in the heart, two of them were discovered and called Wisper and Fixer. In here we sought to investigate their role in renovascular hypertension and their potential as target of cardiac anti-fibrotic treatment. For this, we subjected adult male mice to the renovascular model of hypertension, one-kidney one- clip (1K1C) which induce cardiac and renal fibrosis as well as cardiac functional remodeling. Under these hypertensive conditions, antisense LNA GapmeR targeting Wisper and Fixer were used as anti-fibrotic treatments. We aim to conclude if these two treatments are specifically reducing cardiac remodeling, without influencing kidney fibrosis. Mice were injected 3 times, once a week, starting 2 days after surgery, in order to knockdown the levels of these two lncRNAs. Control mice were injected with non-specific control GapmeR. After 3 weeks, heart dimensions and function were assessed by echocardiography. Cardiac and renal fibrosis were assessed by histology and quantitative real-time PCR analysis. Despite the stress induced by 1K1C hypertension, we were not able to observe significant fibrosis in the kidneys and the heart. In fact, this experiment suggest that the results obtained here, were not sufficient to draw conclusions on the heart specificity of the anti-lncRNAs treatment (Fixer GapmeRs and Wisper GapmeRs).
Keywords
Renovascular hypertension, fibrosis, long non-coding RNA, GapmeR, Wisper
Create date
07/09/2022 16:57
Last modification date
20/09/2023 6:55
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