Silence of lncRNA XIST represses myocardial cell apoptosis in rats with acute myocardial infarction through regulating miR-449

M. Zhang, H.-Y. Liu, Y.-L. Han, L. Wang, D.-D. Zhai, T. Ma, M.-J. Zhang, C.-Z. Liang, Y. Shen

Heart Center, Aerospace Center Hospital, Beijing, China. mengzhangmd@126.com

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• Cardiology

OBJECTIVE: To study the influences of long non-coding ribonucleic acid (lncRNA) X-inactive specific transcript (XIST) on rats with acute myocardial infarction (AMI), and its regulatory mechanism.

MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were randomly assigned into Sham group, Model group, and lncRNA XIST small interfering RNA (XIST siRNA) group. The AMI rat model was prepared through ligating the left anterior descending coronary artery. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular systolic diameter (LVDs), and left ventricular diastolic diameter (LVDd) of rats were determined using a color Doppler ultrasound system. Reverse transcription-polymerase chain reaction was performed to measure the expression levels of lncRNA XIST, microRNA (miR)-449, and Notch1 in rat heart tissues in each group. Pathological morphology of rat heart tissues in each group was observed via hematoxylin-eosin (HE) staining. Cell apoptosis in rat heart tissues was evaluated through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.

RESULTS: Compared with those in Sham group, rats in Model group had significantly increased LVEDV, LVESV, LVDs, and LVDd. After transfection with lncRNA XIST siRNA, XIST level in rat heart tissues was remarkably declined in XIST siRNA group compared with that in Model group. According to HE staining results, the pathological injuries in rat heart tissues were greatly improved in XIST siRNA group compared with those in Model group. TUNEL staining results revealed that the apoptosis rate of cells in rat heart tissues in XIST siRNA group was markedly lower than that in Model group. Higher level of miR-449 and lower level of Notch1 were observed in rats of XIST siRNA group than those of Model group.

CONCLUSIONS: Knockdown of lncRNA XIST can repress the myocardial cell apoptosis in AMI model rats by downregulating miR-449 level.

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