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Plasma levels of microRNA-499 provide an early indication of perioperative myocardial infarction in coronary artery bypass graft patients.

Yao Y, Du J, Cao X, Wang Y, Huang Y, Hu S, Zheng Z - PLoS ONE (2014)

Bottom Line: Importantly, miR levels peaked as early as 1-3 hours, whereas cTnI levels peaked at 6 hours after declamping.Peak plasma concentrations of miRs correlated significantly with cTnI (miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r = 0.437, P = 0.05), indicating the degree of myocardial damage.The data analysis revealed that miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR-499 could be an independent risk factor for PMI.

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Peking, China; Department of Cardiac Surgery, Fuwai Hospital and Cardiovascular Institute, Peking, China; Key Laboratory of Cardiac Regenerative Medicine, Ministry of Health, National Center for Cardiovascular Diseases, Peking, China.

ABSTRACT

Background: Recent studies indicated that microRNAs (miRNAs, miRs) were important for many biological and pathological processes, and they might be potential biomarkers for cardiovascular diseases. The present study aims to determine the release patterns of miRNAs in cardiac surgery and to analyze the ability of miRs to provide early prediction of perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery.

Methodology/principal findings: Thirty on-pump CABG patients were recruited in this study; and miR-499, miR-133a and miR-133b, cardiac troponin I (cTnI) were selected for measurement. Serial plasma samples were collected at seven perioperative time points (preoperatively, and 1, 3, 6, 12, 24, and 48 hours after declamping) and were tested for cTnI and miRs levels. Importantly, miR levels peaked as early as 1-3 hours, whereas cTnI levels peaked at 6 hours after declamping. Peak plasma concentrations of miRs correlated significantly with cTnI (miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r = 0.437, P = 0.05), indicating the degree of myocardial damage. In addition, 30 off-pump CABG patients were recruited; miR-499 and miR-133a levels were tested, which were significantly lower in off-pump group than in on-pump group. A prospective cohort of CABG patients (n = 120) was recruited to study the predictive power of miRs for PMI. The diagnosis of PMI strictly adhered to the principles of universal definition of myocardial infarction. The data analysis revealed that miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR-499 could be an independent risk factor for PMI.

Conclusion: Our results demonstrate that circulating miR-499 is a novel, early biomarker for identifying perioperative myocardial infarction in cardiac surgery.

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Plasma miR and troponin I levels from 29 patients undergoing on-pump CABG (Step I).(A–C) Mean concentrations of circulating miRs expressed as the fold increase (2−ΔΔCt scale) relative to those at the preoperative time point. On average, miR-499, miR-133a, and miR-133b exhibited a 20- to 70-fold increase in plasma samples collected 1 h and 3 h after declamping, respectively. At 48 h after declamping, the values were back to levels comparable to those in the preoperative control. (D–F) Comparison of miRs and cTnI levels in the same plasma samples showing that miR-499, miR-133a and miR-133b peaked earlier than cTnI. (*P<0.01; $P<0.05 vs. control) (G–I) Correlations between the maximum levels of miRs and cTnI. MiR-499 (G), miR-133a (H) and miR-133b (I) correlated significantly with cTnI levels (respectively P<0.001; P<0.01 and P<0.05).
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pone-0104618-g002: Plasma miR and troponin I levels from 29 patients undergoing on-pump CABG (Step I).(A–C) Mean concentrations of circulating miRs expressed as the fold increase (2−ΔΔCt scale) relative to those at the preoperative time point. On average, miR-499, miR-133a, and miR-133b exhibited a 20- to 70-fold increase in plasma samples collected 1 h and 3 h after declamping, respectively. At 48 h after declamping, the values were back to levels comparable to those in the preoperative control. (D–F) Comparison of miRs and cTnI levels in the same plasma samples showing that miR-499, miR-133a and miR-133b peaked earlier than cTnI. (*P<0.01; $P<0.05 vs. control) (G–I) Correlations between the maximum levels of miRs and cTnI. MiR-499 (G), miR-133a (H) and miR-133b (I) correlated significantly with cTnI levels (respectively P<0.001; P<0.01 and P<0.05).

Mentions: The circulating levels of miR-499, as indicated by the fold-change values, were highly elevated at 1, 3, and 6 h after declamping in CABG patients. The levels were 23-fold (P<0.01), 72-fold (P<0.01), and 25-fold (P<0.01) higher, respectively, than the preoperative control level (Fig. 2A). Strikingly, the increased circulating level of miR-499 was restored back to the control value by 48 h after declamping (2-fold, P>0.05, Fig. 2A). MiR-133a and miR-133b levels also increased, though to a lesser extent (Fig. 2B, C).


Plasma levels of microRNA-499 provide an early indication of perioperative myocardial infarction in coronary artery bypass graft patients.

Yao Y, Du J, Cao X, Wang Y, Huang Y, Hu S, Zheng Z - PLoS ONE (2014)

Plasma miR and troponin I levels from 29 patients undergoing on-pump CABG (Step I).(A–C) Mean concentrations of circulating miRs expressed as the fold increase (2−ΔΔCt scale) relative to those at the preoperative time point. On average, miR-499, miR-133a, and miR-133b exhibited a 20- to 70-fold increase in plasma samples collected 1 h and 3 h after declamping, respectively. At 48 h after declamping, the values were back to levels comparable to those in the preoperative control. (D–F) Comparison of miRs and cTnI levels in the same plasma samples showing that miR-499, miR-133a and miR-133b peaked earlier than cTnI. (*P<0.01; $P<0.05 vs. control) (G–I) Correlations between the maximum levels of miRs and cTnI. MiR-499 (G), miR-133a (H) and miR-133b (I) correlated significantly with cTnI levels (respectively P<0.001; P<0.01 and P<0.05).
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pone-0104618-g002: Plasma miR and troponin I levels from 29 patients undergoing on-pump CABG (Step I).(A–C) Mean concentrations of circulating miRs expressed as the fold increase (2−ΔΔCt scale) relative to those at the preoperative time point. On average, miR-499, miR-133a, and miR-133b exhibited a 20- to 70-fold increase in plasma samples collected 1 h and 3 h after declamping, respectively. At 48 h after declamping, the values were back to levels comparable to those in the preoperative control. (D–F) Comparison of miRs and cTnI levels in the same plasma samples showing that miR-499, miR-133a and miR-133b peaked earlier than cTnI. (*P<0.01; $P<0.05 vs. control) (G–I) Correlations between the maximum levels of miRs and cTnI. MiR-499 (G), miR-133a (H) and miR-133b (I) correlated significantly with cTnI levels (respectively P<0.001; P<0.01 and P<0.05).
Mentions: The circulating levels of miR-499, as indicated by the fold-change values, were highly elevated at 1, 3, and 6 h after declamping in CABG patients. The levels were 23-fold (P<0.01), 72-fold (P<0.01), and 25-fold (P<0.01) higher, respectively, than the preoperative control level (Fig. 2A). Strikingly, the increased circulating level of miR-499 was restored back to the control value by 48 h after declamping (2-fold, P>0.05, Fig. 2A). MiR-133a and miR-133b levels also increased, though to a lesser extent (Fig. 2B, C).

Bottom Line: Importantly, miR levels peaked as early as 1-3 hours, whereas cTnI levels peaked at 6 hours after declamping.Peak plasma concentrations of miRs correlated significantly with cTnI (miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r = 0.437, P = 0.05), indicating the degree of myocardial damage.The data analysis revealed that miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR-499 could be an independent risk factor for PMI.

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Peking, China; Department of Cardiac Surgery, Fuwai Hospital and Cardiovascular Institute, Peking, China; Key Laboratory of Cardiac Regenerative Medicine, Ministry of Health, National Center for Cardiovascular Diseases, Peking, China.

ABSTRACT

Background: Recent studies indicated that microRNAs (miRNAs, miRs) were important for many biological and pathological processes, and they might be potential biomarkers for cardiovascular diseases. The present study aims to determine the release patterns of miRNAs in cardiac surgery and to analyze the ability of miRs to provide early prediction of perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery.

Methodology/principal findings: Thirty on-pump CABG patients were recruited in this study; and miR-499, miR-133a and miR-133b, cardiac troponin I (cTnI) were selected for measurement. Serial plasma samples were collected at seven perioperative time points (preoperatively, and 1, 3, 6, 12, 24, and 48 hours after declamping) and were tested for cTnI and miRs levels. Importantly, miR levels peaked as early as 1-3 hours, whereas cTnI levels peaked at 6 hours after declamping. Peak plasma concentrations of miRs correlated significantly with cTnI (miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r = 0.437, P = 0.05), indicating the degree of myocardial damage. In addition, 30 off-pump CABG patients were recruited; miR-499 and miR-133a levels were tested, which were significantly lower in off-pump group than in on-pump group. A prospective cohort of CABG patients (n = 120) was recruited to study the predictive power of miRs for PMI. The diagnosis of PMI strictly adhered to the principles of universal definition of myocardial infarction. The data analysis revealed that miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR-499 could be an independent risk factor for PMI.

Conclusion: Our results demonstrate that circulating miR-499 is a novel, early biomarker for identifying perioperative myocardial infarction in cardiac surgery.

Show MeSH
Related in: MedlinePlus