MicroRNA-34a regulates cardiac ageing and function
Top Cited Papers
- 20 February 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 495 (7439), 107-110
- https://doi.org/10.1038/nature11919
Abstract
Ageing is the predominant risk factor for cardiovascular diseases(1) and contributes to a significantly worse outcome in patients with acute myocardial infarction(2). MicroRNAs (miRNAs) have emerged as crucial regulators of cardiovascular function and some miRNAs have key roles in ageing(3,4). We propose that altered expression of miRNAs in the heart during ageing contributes to the age-dependent decline in cardiac function. Here we show that miR-34a is induced in the ageing heart and that in vivo silencing or genetic deletion of miR-34a reduces age-associated cardiomyocyte cell death. Moreover, miR-34a inhibition reduces cell death and fibrosis following acute myocardial infarction and improves recovery of myocardial function. Mechanistically, we identified PNUTS (also known as PPP1R10) as a novel direct miR-34a target, which reduces telomere shortening, DNA damage responses and cardiomyocyte apoptosis, and improves functional recovery after acute myocardial infarction. Together, these results identify age-induced expression of miR-34a and inhibition of its target PNUTS as a key mechanism that regulates cardiac contractile function during ageing and after acute myocardial infarction, by inducing DNA damage responses and telomere attrition.Keywords
This publication has 36 references indexed in Scilit:
- Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart functionProceedings of the National Academy of Sciences of the United States of America, 2012
- MicroRNAs in the p53 network: micromanagement of tumour suppressionNature Reviews Cancer, 2012
- BRCA1 is an essential regulator of heart function and survival following myocardial infarctionNature Communications, 2011
- MicroRNA‐18 and microRNA‐19 regulate CTGF and TSP‐1 expression in age‐related heart failureAging Cell, 2011
- Pervasive roles of microRNAs in cardiovascular biologyNature, 2011
- Krüppel-like factor 2 improves neovascularization capacity of aged proangiogenic cellsEuropean Heart Journal, 2010
- MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in MiceScience, 2009
- Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area- and length-based approachesJournal of Applied Physiology, 2007
- [48] Production and purification of recombinant adeno-associated virusMethods in Enzymology, 2000
- p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2Science, 1999