Downregulation of miR-151-5p Contributes to Increased Susceptibility to Arrhythmogenesis during Myocardial Infarction with Estrogen Deprivation
| العنوان: | Downregulation of miR-151-5p Contributes to Increased Susceptibility to Arrhythmogenesis during Myocardial Infarction with Estrogen Deprivation |
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| المؤلفون: | Zhengang Bi, Renjun Wang, Xuelian Li, Xue Liu, Hongli Shan, Lei Yang, Yanjie Lu, Zhenwei Pan, Weijie Du, Shaonan Yu, Xuehui Xiong, Hua He, Ying Zhang, Shuxuan Wang, Yongfang Shi |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 9, p e72985 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | medicine.medical_specialty, medicine.drug_class, Heart Ventricles, Intracellular Space, Myocardial Infarction, Myocardial Ischemia, Phospholemman, lcsh:Medicine, Action Potentials, Down-Regulation, Cell Line, Downregulation and upregulation, Internal medicine, Animals, Humans, Medicine, Myocyte, Genetic Predisposition to Disease, Myocytes, Cardiac, Myocardial infarction, Potassium Channels, Inwardly Rectifying, lcsh:Science, Calcium metabolism, Multidisciplinary, business.industry, lcsh:R, Arrhythmias, Cardiac, Estrogens, Transfection, medicine.disease, Rats, Disease Models, Animal, MicroRNAs, Protein Transport, Endocrinology, Animals, Newborn, Gene Expression Regulation, Estrogen, Myocardial infarction complications, lcsh:Q, Calcium, Female, business, Research Article, Protein Binding |
| الوصف: | Estrogen deficiency is associated with increased incidence of cardiovascular diseases. But merely estrogen supplementary treatment can induce many severe complications such as breast cancer. The present study was designed to elucidate molecular mechanisms underlying increased susceptibility of arrhythmogenesis during myocardial infarction with estrogen deprivation, which provides us a new target to cure cardiac disease accompanied with estrogen deprivation. We successfully established a rat model of myocardial ischemia (MI) accompanied with estrogen deprivation by coronary artery ligation and ovariectomy (OVX). Vulnerability and mortality of ventricular arrhythmias increased in estrogen deficiency rats compared to non estrogen deficiency rats when suffered MI, which was associated with down-regulation of microRNA-151-5p (miR-151-5p). Luciferase Reporter Assay demonstrated that miR-151-5p can bind to the 3'-UTR of FXYD1 (coding gene of phospholemman, PLM) and inhibit its expression. We found that the expression of PLM was increased in (OVX+MI) group compared with MI group. More changes such as down-regulation of Kir2.1/IK1, calcium overload had emerged in (OVX+MI) group compared to MI group merely. Transfection of miR-151-5p into primary cultured myocytes decreased PLM levels and [Ca(2+)]i, however, increased Kir2.1 levels. These effects were abolished by the antisense oligonucleotides against miR-151-5p. Co-immunoprecipitation and immunofluorescent experiments confirmed the co-localization between Kir2.1 and PLM in rat ventricular tissue. We conclude that the increased ventricular arrhythmias vulnerability in response to acute myocardial ischemia in rat is critically dependent upon down-regulation of miR-151-5p. These findings support the proposal that miR-151-5p could be a potential therapeutic target for the prevention of ischemic arrhythmias in the subjects with estrogen deficiency. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae3bb812f76872184beb81b7ea6b48a9Test https://doi.org/10.1371/journal.pone.0072985Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ae3bb812f76872184beb81b7ea6b48a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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