PMID- 31841208 OWN - NLM STAT- MEDLINE DCOM- 20201015 LR - 20201015 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 23 IP - 23 DP - 2019 Dec TI - LncRNA MALAT1 knockdown alleviates myocardial apoptosis in rats with myocardial ischemia-reperfusion through activating PI3K/AKT signaling pathway. PG - 10523-10531 LID - 19693 [pii] LID - 10.26355/eurrev_201912_19693 [doi] AB - OBJECTIVE: To observe the effect of long non-coding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) on the myocardial ischemia-reperfusion (I/R) injury in rats and to explore its potential mechanism, to provide certain references for clinical prevention and treatment of myocardial I/R injury. MATERIALS AND METHODS: A total of 60 male Wistar rats were randomly divided into the Control group (n=20), I/R group (n=20) and I/R + MALAT1 small-interfering RNA (siRNA) group (n=20) using a random number table. The I/R model was established through recanalization after ligation of left anterior descending coronary artery (LAD), and the MALAT1 knockdown model was established via tail intravenous injection of MALAT1 siRNA in the I/R + MALAT1 siRNA group. The ejection fraction (EF%) and fractional shortening (FS%) of rats in each group were detected via echocardiography and the infarction area in each group was detected using 2,3,5-triphenyl tetrazolium chloride (TTC) assay. Moreover, the morphological changes in myocardial cells in each group were detected via hematoxylin-eosin (H&E) staining, and the myocardial apoptosis level was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. At the same time, the expression levels of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and pro-apoptotic protein Bcl-2 associated X protein (Bax) in myocardial tissues in each group were determined via Western blotting. Finally, the effect of MALAT1 knockdown on the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) protein expression was detected via Western blotting. RESULTS: The expression level of lncRNA MALAT1 in myocardial tissues was significantly higher in the I/R group than that in the Control group (p<0.05). The MALAT1 knockdown could significantly improve the cardiac insufficiency caused by I/R injury, and increase both EF% and FS% in rats (p<0.05). In addition, the MALAT1 knockdown could markedly inhibit myocardial infarction caused by I/R injury and reduce the infarction area from (62.12 +/- 1.29) to (27.66 +/- 3.58; p<0.05). The results of the H&E staining showed that the myofilaments were arranged more orderly, the degrees of degradation and necrosis were lower and the cellular edema was significantly alleviated in the I/R + MALAT1 siRNA group compared with those in the I/R group. According to the results of TUNEL staining, the rats in I/R + MALAT1 siRNA group had a markedly lower level of myocardial apoptosis than the I/R group (p<0.05), and the Bax/Bcl-2 ratio also remarkably declined in the I/R + MALAT1 siRNA group (p<0.05). Furthermore, the results of Western blotting revealed that MALAT1 siRNA could significantly reverse the I/R injury-induced inhibition on the AKT phosphorylation (p<0.05). CONCLUSIONS: The MALAT1 knockdown can markedly improve the I/R-induced myocardial injury and promote the cardiac function of rats, whose mechanism may be related to the activation of the AKT signaling pathway by MALAT1 siRNA. Therefore, lncRNA MALAT1 is expected to be a new therapeutic target for myocardial I/R injury. FAU - Sun, T AU - Sun T AD - Division of Cardiology, Anzhen Hospital Capital Medical University, Beijing, China. hjzhang73@126.com. FAU - Cheng, Y-T AU - Cheng YT FAU - Yan, L-X AU - Yan LX FAU - Krittanawong, C AU - Krittanawong C FAU - Qian, W AU - Qian W FAU - Zhang, H-J AU - Zhang HJ LA - eng PT - Journal Article PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - 0 (MALAT1 long noncoding RNA, rat) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Small Interfering) RN - EC 2.7.11.1 (Akt1 protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Apoptosis/*genetics MH - Disease Models, Animal MH - Echocardiography MH - Gene Knockdown Techniques MH - Heart/diagnostic imaging MH - Male MH - Myocardial Infarction/*complications/diagnosis/pathology/therapy MH - Myocardial Reperfusion Injury/diagnosis/*genetics/pathology/prevention & control MH - Myocardium/pathology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Long Noncoding/genetics/*metabolism MH - RNA, Small Interfering/administration & dosage MH - Rats MH - Rats, Wistar MH - Signal Transduction/*genetics EDAT- 2019/12/17 06:00 MHDA- 2020/10/21 06:00 CRDT- 2019/12/17 06:00 PHST- 2019/12/17 06:00 [entrez] PHST- 2019/12/17 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] AID - 19693 [pii] AID - 10.26355/eurrev_201912_19693 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10523-10531. doi: 10.26355/eurrev_201912_19693.