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. 2013 Jun 21:11:154.
doi: 10.1186/1479-5876-11-154.

The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury

Han Qin, Guang-xian Chen, Meng-ya Liang, Jian Rong, Jian-ping Yao, Hai Liu, Zhong-kai Wu

The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury

Han Qin et al. J Transl Med. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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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Figures

Figure 1
Figure 1
Experimental protocol. T1: Baseline, after thoractomy, T2: at 60 minutes after aortic clamping, T3: at 25 minutes after reperfusion, and T4: at 90 minutes after reperfusion.
Figure 2
Figure 2
(A and B) The levels of blood CK-MB and cTnT are significantly increased after CPB and reperfusion. P <0.001 were found between T1 vs.T2, T1vs.T3, T1vs.T4.
Figure 3
Figure 3
A comparison of fold changes based on qRT-PCR analysis of mir-499 of 4 time points. (T1 vs. T4). Mir-499 was down-regulated after 90 minutes reperfusion (T4) compared with baseline (T1). (*P = 0.029).
Figure 4
Figure 4
(A and B) Correlation plots between cTnT, CK-MB levels and mir-499 nominal CT values in all 52 samples (all 4 time points). Higher CT value means lower mir-499 expression. The higher the cardiac enzymes, the higher the nominal CT value of mir-499 thus the lower the mir-499 expression level. (A) mir-499 vs. cTnT (r = 0.469, p < 0.001). (B) mir-499 vs. CK-MB (r = 0.273, p = 0.050).
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