title: 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.
authors.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.
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Han
authors.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.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: †Department of Cardiology, Shanxi Province People's Hospital, Taiyuan 030012, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Liu
authors.affiliation: ‡Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Guo
authors.affiliation: §Department of Cardiology, Beijing Xuanwu Hospital Affiliated to Capital Medical University, Beijing 100053, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hua
authors.affiliation: ║Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Yu
authors.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.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: ║Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Yan-Zong
authors.initials: YZ
authors.lastname: Yang
authors.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.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: ║Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Xia
authors.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.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D003598:Cytoskeletal Proteins / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009124:Muscle Proteins / Q000097:blood / Q000235:genetics; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis*; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000097:blood / Q000235:genetics; D000070584:Tripartite Motif Proteins; D019210:Troponin I / Q000097:blood; D044767:Ubiquitin-Protein Ligases / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D003598:Cytoskeletal Proteins; D007527:Isoenzymes; C586302:KLHL41 protein, human; D009124:Muscle Proteins; C485888:TRIM54 protein, human; D000070584:Tripartite Motif Proteins; D019210:Troponin I; C440907:FBXO32 protein, human; C000595665:RNF207 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases