MicroRNA-34a regulates cardiac ageing and function
- PMID: 23426265
- DOI: 10.1038/nature11919
MicroRNA-34a regulates cardiac ageing and function
Abstract
Ageing is the predominant risk factor for cardiovascular diseases and contributes to a significantly worse outcome in patients with acute myocardial infarction. MicroRNAs (miRNAs) have emerged as crucial regulators of cardiovascular function and some miRNAs have key roles in ageing. 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.
Comment in
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miRNAGE-34 induces cardiac damAGE.Cell Res. 2013 Jul;23(7):866-7. doi: 10.1038/cr.2013.57. Epub 2013 Apr 23. Cell Res. 2013. PMID: 23609795 Free PMC article.
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miR-34a and the cardiomyopathy of senescence: SALT PNUTS, SALT PNUTS!Cell Metab. 2013 May 7;17(5):629-30. doi: 10.1016/j.cmet.2013.04.004. Cell Metab. 2013. PMID: 23663732 Free PMC article.
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Keep PNUTS in your heart.Circ Res. 2013 Jul 5;113(2):97-9. doi: 10.1161/CIRCRESAHA.113.301933. Circ Res. 2013. PMID: 23833289
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MicroRNA-34a: a new piece in the cardiac aging puzzle.Circ Cardiovasc Genet. 2013 Aug;6(4):437-8. doi: 10.1161/CIRCGENETICS.113.000277. Circ Cardiovasc Genet. 2013. PMID: 23963163 No abstract available.
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