Cardiac contractility modulation improves left ventricular systolic function partially via miR-25 mediated SERCA2A expression in rabbit trans aortic constriction heart failure model
Cardiac contractility modulation improves left ventricular systolic function partially via miR-25 mediated SERCA2A expression in rabbit trans aortic constriction heart failure model
复制标题
在兔经主动脉缩窄心力衰竭模型中，心脏收缩力调节部分通过 miR-25 介导的 SERCA2A 表达改善左心室收缩功能。
DOI：
10.21037/jtd.2018.06.22
复制
发表时间：
2018-06-01
影响因子：
2.5
通讯作者：
Qi, Guoxian
中科院分区：
文献类型：
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作者：
Chen, Hongyun;Liu, Shuang;Qi, Guoxian
本研究旨在探讨心肌收缩力调节（CCM）改善经主动脉缩窄（TAC）所致心力衰竭（HF）左室收缩功能的机制。将25只新西兰白色家兔随机分为5组：假手术组（SHM）、TAC诱导HF组（HF）、TAC诱导HF + CCM刺激组（HF + CCM），TAC诱导的HF随后注射抗miR-25组（HF + anti-miR-25）、TAC诱导的HF随后CCM刺激和AAV 9-miR-25注射组（HF + CCM + miR-25）。CCM电流每天进行6小时，持续4周。超声检测左室射血分数（LVEF）。逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法用于测量RNA和蛋白质水平。与SHM组相比，HF组心肌肌浆网钙ATP酶（SERCA 2A）和LVEF降低，而miR-25表达增加。相反，与HF组相比，HF + CCM和HF + anti-miR-25组的SERCA 2A和LVEF得到改善，miR-25减少。此外，与HF + CCM组相比，HF + CCM + miR-25组的SERCA 2A和LVEF降低，而miR-25改善。CCM是一种改善左室收缩功能的潜在有效方法，其可能部分通过抑制miR-25表达，进一步改善TAC HF模型中SERCA 2A的表达。
The purpose of this study was to investigate the underlying mechanism of cardiac contractility modulation (CCM) in improving trans aortic constriction (TAC)-induced heart failure (HF) left ventricular (LV) systolic function. A total of 25 New Zealand white rabbits were randomly divided into 5 groups: sham operation group (SHM), TAC-induced HF group (HF), TAC-induced HF followed by CCM stimulation group (HF + CCM), TAC-induced HF followed by injection of anti-miR-25 group (HF + anti-miR-25), TAC-induced HF followed by CCM stimulation and AAV9-miR-25 injection group (HF + CCM + miR-25). CCM current was performed 6 hours a day for 4 weeks. The left ventricle ejection fraction (LVEF) was measured by ultrasound. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used for measuring RNA and protein levels. The sarcoplasmic reticulum calcium ATPase (SERCA2A) and LVEF were reduced, while the miR-25 expression was improved in HF group compared to SHM group. Conversely, the SERCA2A and LVEF were improved, and the miR-25 reduced in the HF + CCM and the HF + anti-miR-25 groups compared to the HF group. Moreover, the SERCA2A and LVEF were reduced, while the miR-25 was improved in the HF + CCM + miR-25 group compared to the HF + CCM group. CCM is a potentially effective procedure for improving LV systolic function, which might partially by inhibiting miR-25 expression, further improved SERCA2A expression in TAC HF models.