An analysis of the global expression of microRNAs in an experimental model of physiological left ventricular hypertrophy.

Nidiane C Martinelli,Kátia G Santos,Amanda Lopes,Daiane Silvello,Stéfanie Schneider,Michael E Andrades,Andréia Biolo,Carolina R Cohen,Luis E Rohde,Ursula Matte,Nadine Clausell,Mauro A Castro,Luzia Frick,Rajesh Gopalrao Katare

doi:10.1371/journal.pone.0093271

Abstract

BackgroundMicroRNAs (miRs) are a class of small non-coding RNAs that regulate gene expression. Studies of transgenic mouse models have indicated that deregulation of a single miR can induce pathological cardiac hypertrophy and cardiac failure. The roles of miRs in the genesis of physiological left ventricular hypertrophy (LVH), however, are not well understood.ObjectiveTo evaluate the global miR expression in an experimental model of exercise-induced LVH.MethodsMale Balb/c mice were divided into sedentary (SED) and exercise (EXE) groups. Voluntary exercise was performed on an odometer-monitored metal wheels for 35 days. Various tests were performed after 7 and 35 days of training, including a transthoracic echocardiography, a maximal exercise test, a miR microarray (miRBase v.16) and qRT-PCR analysis.ResultsThe ratio between the left ventricular weight and body weight was increased by 7% in the EXE group at day 7 (p<0.01) and by 11% at day 35 of training (p<0.001). After 7 days of training, the microarray identified 35 miRs that were differentially expressed between the two groups: 20 were up-regulated and 15 were down-regulated in the EXE group compared with the SED group (p = 0.01). At day 35 of training, 25 miRs were differentially expressed: 15 were up-regulated and 10 were decreased in the EXE animals compared with the SED animals (p<0.01). The qRT-PCR analysis demonstrated an increase in miR-150 levels after 35 days and a decrease in miR-26b, miR-27a and miR-143 after 7 days of voluntary exercise.ConclusionsWe have identified new miRs that can modulate physiological cardiac hypertrophy, particularly miR-26b, -150, -27a and -143. Our data also indicate that previously established regulatory gene pathways involved in pathological LVH are not changed in physiological LVH.

Highlights

Physiological cardiac hypertrophy is a common adaptation that occurs in the heart during exercise training and leads to morphological changes without overall ventricular dysfunction [1,2]
The cellular and molecular mechanisms involved in the genesis of physiologic cardiac hypertrophy are not as well understood as those implicated in pathological growth, but both processes require the activation of a specific set of genes responsible for cardiomyocyte expansion [3,4,5]
A variety of miRs have been identified as mediators of pathologic cardiac hypertrophy, the pattern of miR expression involved in cardiomyocyte growth after a physiological stimulus such as exercise has not been fully elucidated

Summary

Introduction

Physiological cardiac hypertrophy is a common adaptation that occurs in the heart during exercise training and leads to morphological changes without overall ventricular dysfunction [1,2]. The cellular and molecular mechanisms involved in the genesis of physiologic cardiac hypertrophy are not as well understood as those implicated in pathological growth, but both processes require the activation of a specific set of genes responsible for cardiomyocyte expansion [3,4,5]. MicroRNAs (miRs or miRNAs) are a class of small non-coding RNAs that regulate gene expression by inducing mRNA cleavage or by inhibiting protein translation [6]. Changes in the expression of miRs have been described in almost all cardiovascular disorders [8,9,10], and the specific role of miRs in the genesis of cardiac hypertrophy has received great attention in the last decade. MicroRNAs (miRs) are a class of small non-coding RNAs that regulate gene expression. The roles of miRs in the genesis of physiological left ventricular hypertrophy (LVH), are not well understood

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Conclusion