Abstract
BackgroundMicroRNAs 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.Methods13 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.ResultsStatistically 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.ConclusionMyocardial 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.
Highlights
MicroRNAs are short non-coding RNAs which are about 18–25 nucleotides long and act as negative or positive regulators, primarily post-transcriptionally [1,2]
Myocardial biochemical markers changes during cardiopulmonary bypass and reperfusion As demonstrated in Figure 2A and B, the level of cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) level in blood was raised during ischemia and reperfusion
In principle, the present findings support the hypothesis that microRNAs expression level can be influenced by ischemic reperfusion (IR) injury in CPB models and IR injury resultes in a decreased level of mir-499 during reperfusion
Summary
MicroRNAs are short non-coding RNAs which are about 18–25 nucleotides long and act as negative or positive regulators, primarily post-transcriptionally [1,2]. They have enrolled in various pathological conditions, especially cardiovascular disease [3], including ischemic heart disease [4], heart failure [5], cardiac hypertrophy [6] and arrhythmias [7]. We hypothesized that there are changes in the level of microRNAs in cardioplegic heart compared to their baseline Those microRNAs might be potential targets for myocardial protection in CPB. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury
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