The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury.
The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury.
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DOI：
10.1186/1479-5876-11-154
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发表时间：
2013-06-21
影响因子：
7.4
通讯作者：
Wu ZK
中科院分区：
文献类型：
--
作者：
Qin H;Chen GX;Liang MY;Rong J;Yao JP;Liu H;Wu ZK
MicroRNAs参与了多种心血管疾病尤其是缺血性心脏病的研究，但在体外循环下心肌缺血再灌注损伤过程中microRNA的变化尚不清楚。本研究旨在筛选体外循环犬心肌中microRNA的差异，并探讨其与心肌缺血再灌注损伤的关系。13只健康犬接受体外循环，阻断主动脉60分钟，停跳90分钟，再灌流90分钟。分别于不同时间点采集左室心肌标本、血样及血流动力学数据。将3个组织样本汇集在一起，在体外循环前和再灌流90min后对犬左室心肌组织进行microRNAs芯片实验，并用qRT-PCR进行验证。转流前与转流后比较，差异有统计学意义(T1vs.T4，p = 0.041)。我们在4个不同的时间点(T1和T4，p = 0.029)用定量RT-PCR法进一步检测了所有13只犬的mir-499水平。在所有时间点(r = 0.469，p <； 0.001和r = 0.273，p = 0.050)，miR-499的表达与犬的心肌肌钙蛋白T(CTnT)和肌酸激酶同工酶(CK-MB)水平呈负相关。此外，在再灌流后25分钟和90分钟，mir-499的高表达水平与高dp/dtmax相关。体外循环下心肌缺血再灌注损伤可降低犬左室心肌mir-499的表达水平，提示mir-499有望成为心内直视手术期间心脏保护的潜在治疗靶点。
MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury. 13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation. Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p = 0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p = 0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r = 0.469, p < 0.001 and r = 0.273, p = 0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion. Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery.
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