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 Asb2in mouse heart, were selected for the present study. In the AMI rats, the levels of five E3 ligases including Rnf207, Fbxo32, Trim54, Trim63 and Kbtbd10in the plasma were significantly increased compared with control animals. Especially, the plasma levels of Rnf207 was markedly increased at 1h, peaked at 3h and decreased at 624h 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 Rnf207in plasma may be a novel and sensitive biomarkers for AMI in humans.

... 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 Asb2in mouse heart, were selected for the present study. In the AMI rats, the levels of five E3 ligases including Rnf207, Fbxo32, Trim54, Trim63 and Kbtbd10in the plasma were significantly increased compared with control animals. Especially, the plasma levels of Rnf207 was markedly increased at 1h, peaked at 3h and decreased at 624h 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 Rnf207in plasma may be a novel and sensitive biomarkers for AMI in humans. Because of the delayed release of troponins, early diagnosis of acute myocardial infarction (AMI) is a problem. E3 ligase Rnf207 showed higher sensitivity and specificity for diagnosis of AMI. Therefore, We concluded Rnf207 may be a novel biomarkers for AMI. acute myocardial infarction blood biomarkers E3 ubiquitin ligases Rnf207 AMI, acute myocardial

... prognosis for cancer diseases [ 30 ]. However, little is known about whether E3 ligases can serve as early and specific biomarkers of AMI. In the present study, we hypothesized that the cardiac-specific E3 ligases might be released into the circulating blood during AMI, and could be used to predict the myocardial damage. We measured the cardiac-specific E3 ligases in blood from rat models and patients after AMI. Our results identified circulating E3 ligase Rnf207 that can serve as a novel sensitive

... heart, we also detected the expression of those E3 ligases in other major organs, including skeletal muscle, liver, spleen and lung. qPCR analysis revealed that Rnf207 was greatly and specifically expressed in the heart. Asb11, Trim54, Kbtbd10, Trim63 and Fbxo32 were predominantly expressed in the heart and skeletal muscle, some of them are in agreement with previous reports [ 27 , 34 36 ]. Others including Asb2, Cish, Lmo7, Apc and so on were expressed in different tissues ( Figure 1 B). We therefore chose Rnf207, Fbxo32, Trim54, Trim63, Kbtbd10 and Asb11 as candidate biomarkers of AMI. Cardiac-specific E3 ligases are increased in blood from AMI rats To investigate whether cardiac E3 ligases can be released into blood and be detected with their increase in circulating blood after AMI, we generated an AMI rat model by left coronary artery ligation. Rat cardiac severity and function were evaluated with TTC staining and echocardiography at 24h of ligation, respectively. We found that the

... high level until 24h ( Figure 2 A). Notably, the plasma levels of Rnf207 and Fbxo32 were also markedly increased (1.6- or 1.9-fold, respectively) at 1h, peaked (2.8- or 2.2-fold, respectively) at 3h and decreased at 624h after ligation, whereas the plasma levels of Trim54, Trim63, and Kbtbd10 did not increase at 1h, but significantly increased at 3h, then decreased to baseline at 624h ( Figure 2 A). The levels of Asb11 did not change considerably during the AMI procedure. Interestingly, the levels

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Gene: RNF207 - ring finger protein 207 - (NCBI)

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