Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute
myocardial infarction
#MMPMID25599194
Han QY
; Wang HX
; Liu XH
; Guo CX
; Hua Q
; Yu XH
; Li N
; Yang YZ
; Du J
; Xia YL
; Li HH
Clin Sci (Lond)
2015[Jun]; 128
(11
): 751-60
PMID25599194
show ga
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.