The Expression Changes Of Long Non-Coding RNAs On Pressure Overload-induced Myocardial Hypertrophy

ObjectiveMyocardial hypertrophy is a compensatory response to pathological stimuli, which is mainly caused by long-term cardiac overload. However, long-term stimulations eventually leads to heart failure （HF）.However, the detailed mechanism of signal transduction molecules is still preliminary.Long non-coding RNA （IncRNA） is defined as a class of ncRNA which length is longer than 200nt and have no open reading frame encoding proteins. It has been demonstrated to play pivotal roles in multiple biological process and is increasing recognized as contributors to the pathology of cancer, neurodegenerative diseases, heart diseases and so on. However, the expression profile of lncRNA in myocardial hypertrophy remains unclear.In order to investigate long noncoding RNAs on myocardial hypertrophy and study the molecular mechanism, we took advantage of microarray analysis to test the differentially expressed lncRNAs in rat cardiac hypertrophy induced by transverse aortic constriction （TAC）. After bioinformatics analysis, the differentially expressed IncRNAs in rat cardiac hypertrophy induced by TAC were screened out.Methods10 male Wistar rats whose weight were about 180-220g were randomly divided into 2 groups:sham-operated （Sham） rats and abdominal aortic constriction （AAC） rats. There are 5 rats in each group.4 weeks after surgery, the form of heart were examined by colour doppler ultrasonic diagnostic instrument and HE staining. Quantificational real-time polymerase chain reaction （qRT-PCR） was used to identify the expression levels of ANF andβ-MHC mRNA. It’s sure that the cardiac hypertrophy model was successfully constructed, the lncRNA expression profile in abdominal aortic constriction rats were tested by lncRNA microarray. Afterwards the raw results were bioinformaticly analyzed to select the differentially expressed lncRNAs, the qRT-PCR was used to test the related differential lncRNAs. After the consequential bioinformatics analysis, the association networks between the antisense lncRNA XR₀08680 and target genes were constructed.Results1. Compared to SH rats, the ratio of left ventricular weight to body weight （the left ventricular mass index, LVMI）, left ventricular ejection fraction （LVEF）,diastolic left ventricular posterior wall thickness （LVPWd） and the size of myocyte were significantly increased（/><0.05）.The level of expression of ANF、β-MHC mRNA in AAC rats were significantly increased（P<0.05） compared to SH ones. The results proved that myocardial hypertrophy model was built successfully.2. By using Arraystar 4×44K Rat LncRNA Array,6969 LncRNAs and 12324 mRNAs were detected. Among these lncRNAs,252 lncRNAs were significantly differentially expressed including 80 up-regulated and 172 down-regulated by set a filter of fold-change>2.0 and each P<0.05. Meanwhile,451 differently expressed mRNAs were identified which containing 208 up-regulated and 243 down-regulated.5 lncRNAs were validated by qRT-PCR, the results and microarray data are accordant.3. GO analysis indicaded that the mRNAs were mainly referred to immune system and stress,the pathway anlysis showed that play roles in cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway and NF-kappa B signaling pathway.4. Bioinfomatic technique discovered that there were 111 target genes of lncRNA XR₀08680, the target genes include Hspb6, Prmt5 and Edg7 which were associated with Cell proliferation and growth.ConclusionAbdominal aorta constriction induced compensatory myocardial hypertrophy of rats. The expression of lncRNAs on pressure overload-induced myocardial hypertrophy changes significantly in comparison with normal ones. The result may indicate the potential roles of lncRNAs in the regulatory molecular mechanisms in myocardial hypertrophy...