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Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute myocardial infarction.

ABSTRACT: Ubiquitin ligase (E3) is a decisive element of the ubiquitin-proteasome system (UPS), which is the main pathway for intracellular protein turnover. Recently, circulating E3 ligases have been increasingly considered as cancer biomarkers. In the present study, we aimed to determine if cardiac-specific E3 ligases in circulation can serve as novel predictors for early diagnosis of acute myocardial infarction (AMI). By screening and verifying their tissue expression patterns with microarray and real-time PCR analysis, six of 261 E3 ligases, including cardiac-specific Rnf207 and cardiac- and muscle-enriched Fbxo32/atrogin-1, Trim54/MuRF3, Trim63/MuRF1, Kbtbd10/KLHL41, Asb11 and Asb2 in mouse heart, were selected for the present study. In the AMI rats, the levels of five E3 ligases including Rnf207, Fbxo32, Trim54, Trim63 and Kbtbd10 in the plasma were significantly increased compared with control animals. Especially, the plasma levels of Rnf207 was markedly increased at 1 h, peaked at 3 h and decreased at 6-24 h after ligation. Further evaluation of E3 ligases in AMI patients confirmed that plasma Rnf207 level increased significantly compared with that in healthy people and patients without AMI, and showed a similar time course to that in AMI rats. Simultaneously, plasma level of cardiac troponin I (cTnI) was measured by ELISA assays. Finally, receiver operating characteristic (ROC) curve analysis indicated that Rnf207 showed a similar sensitivity and specificity to the classic biomarker troponin I for diagnosis of AMI. Increased cardiac-specific E3 ligase Rnf207 in plasma may be a novel and sensitive biomarkers for AMI in humans.

SUBMITTER: Han QY

PROVIDER: S-EPMC4557400 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute myocardial infarction.

Han Qiu-Yue QY Wang Hong-Xia HX Liu Xiao-Hong XH Guo Cai-Xia CX Hua Qi Q Yu Xiao-Hong XH Li Nan N Yang Yan-Zong YZ Du Jie J Xia Yun-Long YL Li Hui-Hua HH

Clinical science (London, England : 1979) 20150601 11

Ubiquitin ligase (E3) is a decisive element of the ubiquitin-proteasome system (UPS), which is the main pathway for intracellular protein turnover. Recently, circulating E3 ligases have been increasingly considered as cancer biomarkers. In the present study, we aimed to determine if cardiac-specific E3 ligases in circulation can serve as novel predictors for early diagnosis of acute myocardial infarction (AMI). By screening and verifying their tissue expression patterns with microarray and real- ...[more]

PMID: 25599194

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Project description:BACKGROUND: The dysregulated expressions of circulating miRNAs have been detected in various cardiovascular diseases. In our previous experiments, the altered expressions of circulating miRNA-21-5p, miRNA-361-5p and miRNA-519e-5p were confirmed in patients with coronary atherosclerosis by miRNA microarrays. However, the expression levels of these circulating miRNAs in the early phase of acute myocardial infarction (AMI) are still unknown. In the present study, our aims were to examine the expressions of circulating miR-21-5p, miR-361-5p and miR-519e-5p in AMI patients, and assess their clinical applications for diagnosing and monitoring AMI. RESULTS: Two different cohorts were enrolled in this study. The first cohort included 17 AMI patients and 28 healthy volunteers, and the second cohort included 9 AMI patients, 9 ischemic stroke patients, 8 patients with pulmonary embolism, and 12 healthy volunteers. Quantitative real-time PCR and ELISA assays were preformed to detect the concentrations of plasma miRNAs and cardiac troponin I (cTnI), respectively. The results showed that the plasma levels of miR-21-5p and miR-361-5p were significantly increased in AMI patients, whereas the concentration of circulating miR-519e-5p was reduced. Interestingly, the levels of these circulating miRNAs correlated with the concentrations of plasma cTnI. Receiver operating characteristic (ROC) analysis revealed that these three circulating miRNAs had considerable diagnostic accuracy for AMI with high values of area under ROC curve (AUC). Importantly, combining the three miRNAs significantly increased the diagnostic accuracy. Furthermore, cell experiments demonstrated that these plasma miRNAs may originate from injured cardiomyocytes induced by hypoxia. In addition, the levels of all the three circulating miRNAs in ischemic stroke (IS) and pulmonary embolism (PE) were elevated, whereas the decreased level of plasma miR-519e-5p was only detected in AMI. ROC analysis demonstrated that circulating miR-519e-5p may be a useful biomarker for distinguishing AMI from other ischemic diseases. CONCLUSIONS: Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.

Project description:BackgroundAcute myocardial infarction (AMI) is the most serious type of heart disease. Clinically, there is an urgent need to discover diagnostic biomarkers for the early diagnosis of AMI.MethodsSerum proteomic profiles in AMI patients, healthy controls, and stable angina pectoris (SAP) patients were explored and compared by iTRAQ-2DLC-MS/MS. The clinical data of AMI patients were also analyzed. Differentially expressed proteins were validated by enzyme linked immunosorbent assay (ELISA), and diagnostic models were constructed.ResultsA total of 39 differentially expressed proteins were identified in AMI patients. The results showed that the serum levels of apolipoprotein E (APOE) in AMI patients were notably higher than those in the healthy controls (P=0.0172). The serum levels of aspartate aminotransferase (AATC) in AMI patients were markedly higher than those in the healthy controls and SAP patients (P<0.0001 and P<0.0001, respectively). The serum levels of fibronectin (FINC) in SAP patients were significantly higher than those in the healthy controls and AMI patients (P=0.0043 and P=0.0044, respectively). Clinical data analysis showed a considerable difference in blood glucose levels, troponin I (TNI), and creatine kinase (CK) in AMI patients compared with SAP patients and healthy controls. A diagnostic model consisting of AATC and clinical indicators [lactate dehydrogenase (LDH) and CK] was established to distinguish between AMI patients and healthy controls, with an area under the curve (AUC) value of 0.993 sensitivity and specificity of 96.2% and 96.3%, respectively. A diagnostic model consisting of AATC and CK was established to distinguish between AMI patients and SAP patients, with an AUC value of 0.975 and a sensitivity and specificity of 85.2% and 79.30%, respectively.ConclusionsIn this study, differentially expressed proteins in AMI patients were combined with clinical indexes, LDH and CK, and two diagnostic models were constructed. This study may provide meaningful data for the early diagnosis of AMI.

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Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute myocardial infarction.

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Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute myocardial infarction.

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