دورية أكاديمية

Sarcopenia-derived exosomal micro-RNA 16-5p exerts the cardio-repair disturbance via pro-apoptotic mechanism in myocardial infarction of mice

التفاصيل البيبلوغرافية
العنوان: Sarcopenia-derived exosomal micro-RNA 16-5p exerts the cardio-repair disturbance via pro-apoptotic mechanism in myocardial infarction of mice
المؤلفون: Hayasaka, T, Takehara, N, Horiuchi, K, Kano, K, Tomita, Y, Yoshida, Y, Maruyama, K, Minoshima, A, Kawabe, J, Hasebe, N
المصدر: European Heart Journal ; volume 41, issue Supplement_2 ; ISSN 0195-668X 1522-9645
بيانات النشر: Oxford University Press (OUP)
سنة النشر: 2020
مصطلحات موضوعية: Cardiology and Cardiovascular Medicine
الوصف: Background Sarcopenia is a pathophysiological malfunction induced by skeletal muscle atrophy, and several studies reported an association between sarcopenia-induced cardiac cachexia and poor prognosis in heart disease. Since only a few established animal models are recently available, the underlying mechanism of disturbed cardiac repair accompanied with sarcopenia remains poorly understood. Purpose We hypothesized that specific microRNAs in sarcopenia-derived exosomes play crucial roles in disturbed cardiac repair with sarcopenia, and these microRNAs directly exacerbate cardiomyocyte injury following cardiac ischemia and reperfusion. Methods We developed a novel sarcopenia-induced cardiac repair disturbance mouse model that is induced by tail suspension (TS) 7 days after a 45-min coronary occlusion of cardiac ischemia and reperfusion (I/R). The reduction of the left ventricular ejection fraction (LVEF) after I/R was compared in mice with TS [I/R-TS(+), n=14] and without [I/R-TS(−), n=12] by echocardiography. To investigate the exosomal mechanism of cardiac repair disturbance, a comprehensive analysis of extracted exosomal microRNAs from mice serum was performed in the 2 groups at day 8. Then, we investigated the impact of the identified candidate microRNA in neonatal rat cardiomyocytes (NRVMs). After 4 days in primary culture, candidate microRNA was transfected into NRVMs under hypoxic culture conditions. TUNEL analysis and quantitative PCR analysis of apoptosis-related genes were performed on the NRVMs. Results At day 8 after I/R, the LVEF of I/R-TS(+) was not significantly ameliorated compared to that of I/R-TS(−) (ΔLVEF; 1.59±6.92 vs. 8.04±7.71% p=0.034). Four candidate microRNAs obtained from I/R mice serum were identified in the microRNA array analysis. The re-analysis of these candidate micro-RNAs using all I/R mice demonstrated that the level of mir-16-5p in I/R-TS(+) was raised by approximately nine-fold than that in I/R-TS(−) (9.67±13.35 vs. 0.99±1.41, p<0.05). Next, an in vitro ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1093/ehjci/ehaa946.2872
الإتاحة: https://doi.org/10.1093/ehjci/ehaa946.2872Test
http://academic.oup.com/eurheartj/article-pdf/41/Supplement_2/ehaa946.2872/34517404/ehaa946.2872.pdfTest
حقوق: https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_modelTest
رقم الانضمام: edsbas.3477CE28
قاعدة البيانات: BASE