Identification of candidate long noncoding RNAs associated with left ventricular hypertrophy.
OBJECTIVE
Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding RNAs, which regulate gene expression. Their role in cardiac disease is poorly known. Here, we investigated the association between lncRNAs and left ventricular hypertrophy.


METHODS
Wild-type and adenosine A2A receptor overexpressing mice (A2A-Tg) were subjected to transverse aortic constriction (TAC) and expression of lncRNAs in the heart was investigated using genome-wide microarrays and an analytical pipeline specifically developed for lncRNAs.


RESULTS
Microarray analysis identified two lncRNAs up-regulated and three down-regulated in the hearts of A2A-Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs 2900055J20Rik and Gm14005 were decreased in A2A-Tg mice (3.5- and 1.8-fold, p < 0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005 were increased in TAC mice compared to sham-operated animals (1.8- and 1.4-fold, after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2- and 1.6-fold (p < 0.01).


CONCLUSIONS
First, we have shown that data on lncRNAs can be obtained from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and Gm14005 is regulated after TAC and can be modulated by cardioprotective molecules. These observations motivate further investigation of the therapeutic value of lncRNAs in the heart.
Laboratory of Cardiovascular Research, Public Research Center - Health (CRP-Santé), Luxembourg.
Lu
L
Zhang
Eman A
EA
Hamad
Mélanie
M
Vausort
Hajime
H
Funakoshi
Arthur M
AM
Feldman
Daniel R
DR
Wagner
Yvan
Y
Devaux
D000818:Animals; D001011:Aorta / Q000473:pathology; D002316:Cardiotonic Agents / Q000737:chemistry; D016208:Databases, Factual; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding; D043705:Receptor, Adenosine A2A / Q000235:genetics; D019076:Transgenes
D002316:Cardiotonic Agents; D062085:RNA, Long Noncoding; D043705:Receptor, Adenosine A2A
adenosine; cardiac hypertrophy; cardioprotective molecules; experimental disease model; long noncoding RNAs; microarrays