Abstract
BackgroundMicroRNAs (miRNAs) are short, single-stranded and non-coding RNAs, freely circulating in human plasma and correlating with vary pathologies. In this study, we monitored early myocardial injury and recovery after heart transplantation by detecting levels of circulating muscle-specific miR-133a, miR-133b and miR-208a.Methods7 consecutive patients underwent heart transplantation in Fuwai hospital and 14 healthy controls were included in our study. Peripheral vein blood was drawn from patients on the day just after transplantation (day 0), the 1st, 2nd, 3rd, 7th and 14th day after transplantation respectively. Serum from peripheral blood was obtained for cardiac troponin I (cTnI) measurement. Plasma was centrifuged from peripheral blood for measuring miR-133a, miR-133b and miR-208a by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The plasma concentration of miRNAs were calculated by absolute quantification method. The sensitivity and specificity of circulating miRNAs were revealed by receiver operating characteristic curve (ROC) analysis. Correlations between miRNAs and cTnI / perioperative parameters were analyzed.ResultsSimilar to cTnI, miR-133a, miR-133b and miR-208a all showed dynamic changes from high to low levels early after operation. The Sensitivity and specificity of miRNAs were: miR-133a (85.7%,100%), miR-208a (100%,100%), and miR-133b (90%,100%). Correlations between miRNAs and cTnI were statistically significant (p < 0.05), especially for miR-133b (R2 = 0.813, p < 0.001). MiR-133b from Day 0-Day 2 (r > 0.98, p < 0.01), and cTnI from Day 1- Day 3 (r > 0.86, p < 0.05) had strong correlations with bypass time, particularly parallel bypass time. Obviously, miR-133b had a better correlation than cTnI. Circulating miR-133b correlated well with parameters of heart function such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and inotrope support, while cTnI only correlated with 3 of the 4 parameters mentioned above. MiR-133b also had strong correlations with ventilation time (r > 0.99, p < 0.001) and length of ICU stay (r > 0.92, p < 0.05), both of which reflected the recovery after operation. The correlation coefficients of miR-133b were also higher than that of cTnI.ConclusionsThe dynamic change in circulating muscle-specific miRNAs, especially miR-133b can reflect early myocardial injury after heart transplantation. And miR-133b may have advantages over cTnI in forecasting graft dysfunction and recovery of patients after operation.
Highlights
MicroRNAs are short, single-stranded and non-coding RNAs, freely circulating in human plasma and correlating with vary pathologies
There seemed to be no difference for miRNAs in patients compared to controls after 2 days since heart transplantation except miR208a, which was still significant at Day 2 (2852 ± 550 copies/ul, p < 0.05)
Fold changes of miR-133a, miR208a and cardiac troponin I (cTnI) on Day 0 or Day 1 was significantly higher compared to Day 14 (p < 0.05), there were no significance on other time points
Summary
MicroRNAs (miRNAs) are short, single-stranded and non-coding RNAs, freely circulating in human plasma and correlating with vary pathologies. We monitored early myocardial injury and recovery after heart transplantation by detecting levels of circulating muscle-specific miR-133a, miR-133b and miR-208a. MicroRNAs (miRNAs) are single-stranded, non-coding RNAs with a length of 19–25 nucleotides, which negatively regulate gene expression by recognizing complementary messenger RNAs (mRNAs) and prohibiting their translation into functional protein [1]. As the most effective therapy for end-stage heart disease, heart transplantation is widely used in many medical centers. It is very important to monitor the myocardial injury and give medical therapy at the early stage after transplantation. We hypothesized that the dynamic change of cardiomyocyte-enriched miRNAs in peripheral blood could reflect the myocardial injury and predict recovery of heart function after heart transplantation. We measured the circulating levels of miR-133a, miR-208a, and miR-133b in different time point after operation in the context of a sensitive myonecrosis marker, cardiac troponin I (cTnI), in 7 consecutive patients undergone heart transplantation
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