MicroRNA-34a Regulates Cardiac Ageing and Function

Overview

Journal Nature

Specialty Science

Date 2013 Feb 22

PMID 23426265

Citations 387

Authors

Reinier A Boon

Kazuma Iekushi

Stefanie Lechner

Timon Seeger

Ariane Fischer

Susanne Heydt

David Kaluza

Karine Treguer

Guillaume Carmona

Angelika Bonauer

Anton J G Horrevoets

Nathalie Didier

Zenawit Girmatsion

Peter Biliczki

Joachim R Ehrlich

Hugo A Katus

Oliver J Muller

Michael Potente

Andreas M Zeiher

Heiko Hermeking

Stefanie Dimmeler

Affiliations

Soon will be listed here.

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.

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