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

Han QY, Wang HX, Liu XH, Guo CX, Hua Q, Yu XH, Li N, Yang YZ, Du J, Xia YL, Li HH - Clin. Sci. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: *Department of Physiology, Pathology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100069, China.

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.

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Detection of E3 ligases specifically expressed in the mouse heart(A) Microarrays analysis of ubiquitin E3 ligases expression in heart, aorta, kidney and brains from mouse. (B) Real-time PCR analysis of ubiquitin E3 ligases expression in eight organs from mouse (n=9 per group). Sk.M, skeletal muscle.
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Figure 1: Detection of E3 ligases specifically expressed in the mouse heart(A) Microarrays analysis of ubiquitin E3 ligases expression in heart, aorta, kidney and brains from mouse. (B) Real-time PCR analysis of ubiquitin E3 ligases expression in eight organs from mouse (n=9 per group). Sk.M, skeletal muscle.

Mentions: In our preliminary experiments, we first determined which E3 ligases were specifically or highly expressed in the mouse hearts compared with other tissues. The mRNA microarray assays were performed in the heart, kidney, brain and aorta from WT mice. A total 34000 genes were screened, and 261 E3 ligases were detected in four tissues (see Supplementary material online, Table S2). Among them, sixteen E3 ligases that are highly expressed in the heart but lower in the other three tissues, and two E3 ligases that are ubiquitously expressed in four tissues as controls were selected (Table S2, Figure 1A).


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

Han QY, Wang HX, Liu XH, Guo CX, Hua Q, Yu XH, Li N, Yang YZ, Du J, Xia YL, Li HH - Clin. Sci. (2015)

Detection of E3 ligases specifically expressed in the mouse heart(A) Microarrays analysis of ubiquitin E3 ligases expression in heart, aorta, kidney and brains from mouse. (B) Real-time PCR analysis of ubiquitin E3 ligases expression in eight organs from mouse (n=9 per group). Sk.M, skeletal muscle.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4557400&req=5

Figure 1: Detection of E3 ligases specifically expressed in the mouse heart(A) Microarrays analysis of ubiquitin E3 ligases expression in heart, aorta, kidney and brains from mouse. (B) Real-time PCR analysis of ubiquitin E3 ligases expression in eight organs from mouse (n=9 per group). Sk.M, skeletal muscle.
Mentions: In our preliminary experiments, we first determined which E3 ligases were specifically or highly expressed in the mouse hearts compared with other tissues. The mRNA microarray assays were performed in the heart, kidney, brain and aorta from WT mice. A total 34000 genes were screened, and 261 E3 ligases were detected in four tissues (see Supplementary material online, Table S2). Among them, sixteen E3 ligases that are highly expressed in the heart but lower in the other three tissues, and two E3 ligases that are ubiquitously expressed in four tissues as controls were selected (Table S2, Figure 1A).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: *Department of Physiology, Pathology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100069, China.

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.

Show MeSH
Related in: MedlinePlus