Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.

Details

Serval ID
serval:BIB_219FB1ADDEA8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health.
Journal
Scientific reports
Author(s)
Heid J., Cencioni C., Ripa R., Baumgart M., Atlante S., Milano G., Scopece A., Kuenne C., Guenther S., Azzimato V., Farsetti A., Rossi G., Braun T., Pompilio G., Martelli F., Zeiher A.M., Cellerino A., Gaetano C., Spallotta F.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
04/12/2017
Peer-reviewed
Oui
Volume
7
Number
1
Pages
16839
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O <sub>2</sub> levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis.
Keywords
5-Methylcytosine/metabolism, Aging, Animals, Antagomirs/metabolism, Cell Hypoxia, Cell Line, Collagen/metabolism, DNA Methylation, Echocardiography, Fibroblasts/cytology, Fibroblasts/metabolism, Fishes/genetics, Heart/physiology, Humans, MicroRNAs/antagonists & inhibitors, MicroRNAs/genetics, MicroRNAs/metabolism, Myocardium/metabolism, Oxidative Stress, Up-Regulation, Zebrafish
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2017 20:13
Last modification date
20/08/2019 13:58
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