PUBLICATION
Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health
- Authors
- 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.
- ID
- ZDB-PUB-171206-8
- Date
- 2017
- Source
- Scientific Reports 7: 16839 (Journal)
- Registered Authors
- Cellerino, Alessandro
- Keywords
- none
- Datasets
- GEO:GSE107003
- MeSH Terms
-
- 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
- 29203887 Full text @ Sci. Rep.
Citation
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. (2017) Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health. Scientific Reports. 7:16839.
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% O2 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping