Received: 14 May 2018 | Accepted: 26 August 2018

DOI: 10.1002/jcp.27274

ORIGINAL RESEARCH ARTICLE

Circulating miR‐22‐5p and miR‐122‐5p are promising novel

biomarkers for diagnosis of acute myocardial infarction

Yu Wang1 | Wenguang Chang1 | Yuan Zhang1 | Lei Zhang1 | Han Ding1 |

Hongzhao Qi 1
| Sheng Xue 1
| Hua Yu 2
| Longgang Hu 2
| Dacheng Liu 3
|
Wenjie Zhu 3,4
| Yin Wang 1
| Peifeng Li 1

1
Translational Medicine Center, Institute for
Translational Medicine, Qingdao University, Abstract
Qingdao, China Background/Aims: This study sought to evaluate the potential of circulating
2
Department of Cardiovascular Medicine, The
microRNAs (miRNAs) as novel indicators for acute myocardial infarction (AMI).
Affiliated Cardiovascular Hospital of Qingdao
University, Qingdao, China Methods: Plasma samples were collected from each participant, and total RNA was
3
Emergency Department, The Affiliated extracted. Quantitative real‐time polymerase chain reaction were used to investigate
Hospital of Qingdao University, Qingdao,
China the expression of circulating miRNAs. We measured circulating levels of six individual
4
Cardiovascular Surgery Department, The miRNAs, which are known to be relevant to AMI, in the plasma samples from 66 AMI
Affiliated Hospital of Qingdao University,
patients and 70 non‐AMI healthy comparisons.
Qingdao, China
Results: Five small RNAs were specifically expressed in AMI patients, plasma
Correspondence
miR‐122‐5p levels is significantly elevated (p < 0.0001) in AMI patients, while plasma
Yu Wang, Sheng Xue, and Peifeng Li,
Translational Medicine Center, Institute for miR‐22‐5p (p < 0.05) levels were significantly decreased. In addition, significant
Translational Medicine, Qingdao University,
correlations between miR‐22‐5p and miR‐122‐5p (R = 0.773), miR‐122‐5p and
Dengzhou Road 38, Qingdao 266071, Shibei
District, China. creatine kinase isoenzyme (CK‐MB; R = 0.6296) were detected. Further, receiver
Email: 986@163.com (Y. W.);
operating characteristic (ROC) analysis indicated that miR‐22‐5p showed consider-
shengxue198@126.com (S. X.);
peifli@hotmail.com (P. L.) able diagnostic efficiency for predicting AMI (area under the curve [AUC] = 0.975).
Combining miR‐22‐5p and miR‐122‐5p in a panel increased the sensitivity (98.6%) of
Funding information
National Natural Science Foundation of China, distinguishing between patients with AMI and healthy comparisons.
Grant/Award Number: 81700704; National
Conclusion: Circulating miR‐22‐5p and miR‐122‐5p could be considered promising
Natural Science Foundation of China, Grant/
Award Number: 81741173 novel diagnostic biomarkers for AMI.

KEYWORDS
acute myocardial infarction, diagnostic biomarkers, microRNAs, myocardial cell death

1 | INTRODUCTION and effective methods for early diagnosis of AMI remain to be

Acute myocardial infarction (AMI) is one of the cardiovascular
diseases with high morbidity and mortality worldwide. Early rapid
and accurate diagnosis of AMI is urgently needed. Currently,
increasing of creatine kinase isoenzyme (CK‐MB) and troponin
(T or I) are important indicators for the diagnosis of acute myocardial
infarction and has been widely used in clinical diagnosis. However, as
the early diagnosis of AMI’s sensitivity and specificity increases, the
exploration of new biomarkers has never stopped. Low‐cost, timely,
J Cell Physiol. 2018;1–9. wileyonlinelibrary.com/journal/jcp
developed.
MicroRNAs (miRNAs), an endogenetic RNA with a length of about
20–24 nucleotides, which is highly stable in the blood circulation, has
been proved to have an important role in the transcription and
posttranscriptional regulation of gene expression (Ambros, 2004).
Many studies suggest that miRNAs play crucial roles in proliferation,
development, differentiation, and apoptosis (Plasterk, 2006). The
expression levels of the miRNAs are significantly different depending
on tissues and developmental stages. The expression pattern of
© 2018 Wiley Periodicals, Inc. | 1
2 | WANG ET AL.

miRNAs has the characteristics of differentiation, phase, and timing, T A B L E 1 Clinical characteristics of AMI patients and the control
which suggests miRNA has the potential to be an indicator for disease subjects
diagnosis (Wang et al., 2016; Zhang et al., 2015). Control AMI
There are numerous studies which indicated the close relationship Variable group (n = 70) group (n = 66) p
between miRNA and cardiovascular diseases. Studies have shown that Male/female (n/n) 26/44 30/36 –
miR‐19b‐3p inhibits autophagy and apoptosis by targeting transforming Age (years) 61.90 ± 3.69 61.84 ± 1.71 0.76
growth factor, beta receptor II (TGF‐β R II), atrogin‐1, and muscle RING‐ BMI (kg/m ) 2
23.09 ± 1.29 25.71 ± 0.53 0.10
finger protein‐1 (MuRF‐1) in cells (Song, Ryu, Kim, Kwon, & Kim, 2014;
Hypertension, n (%) 5 (7.10%) 35 (53.03%) –
Zou et al., 2016). Gupta et al. (2016) identified that miR‐22 is an
DM, n (%) 0 13 (19.70%) –
abundant and strong inhibitor of the cardiac autophagy, highlighting
9
WBC (×10 /L) 8.91 ± 1.44 7.69 ± 0.57 0.27
miR‐22 as a biomarker candidate for cardiovascular disorders. MiR‐122‐
5p was confirmed as potential regulators of cardiac sarco(endo)plasmic SBP (mmHg) 127.60 ± 4.69 134.58 ± 4.43 0.35

reticulum calcium ATPase‐2, which has a critical role in myocardial DBP (mmHg) 73.10 ± 3.60 77.65 ± 2.31 0.35
contractility (Boštjančič, Zidar, & Glavač, 2012). Nevertheless, miR‐134 Heart rate 81.40 ± 3.36 72.35 ± 1.75 0.02*
and miR‐186‐5p are reported to be upregulated in patients with acute (beats/min)
coronary syndrome (He et al., 2014; Zeller et al., 2014). MiR‐375 as a TC (mmol/L) 4.35 ± 0.66 4.73 ± 0.25 0.53
suitable blood marker to predict diabetes, was detected in acute HDL (mmol/L) 1.12 ± 0.21 1.10 ± 0.05 0.33
ST‐segment elevation MI patients (D’Alessandra et al., 2010; Song, Roels, LDL (mmol/L) 2.60 ± 0.50 2.84 ± 0.22 0.84
Martens, & Bouwens, 2017). These six miRNAs are involved in the
TG (mmol/L) 0.84 ± 0.13 2.31 ± 0.60 0.15
regulation of autophagy and apoptosis in myocardial myocytes during
Cr ( µmol/L) 70.89 ± 7.04 59.65 ± 3.12 0.12
myocardial infarction. In light of these findings, it has been hypothesized
CK‐MB (IU/L) 5.65 ± 1.63 30.83 ± 6.13 0.035*
that miRNAs also may be regarded as biomarkers of cardiac diseases.
The possibility of using miRNAs as a novel myocardial biomarker has Note. Data are shown as the mean ± SE.
*p < 0.05 and **p < 0.01 for AMI group versus control group.
been previously raised. However, the specific expression of these
circulating miRNAs in AMI patients and their clinical significance remain
unknown. In the current study, we have performed frequent (up to six), were diagnosed for the first time, and the age between 18 and
repeated measurements of multiple miRNAs that were previously linked 80 years. Detection of a rise and/or fall of cardiac biomarker values,
to AMI (miR‐122‐5p, miR‐19‐3p, miR‐134‐5p, miR‐186‐5p, and preferably high‐sensitivity troponin (HsTNT) with at least one value
miR‐375) or have been shown to be cardiac enriched (miR‐22‐5p) in above the 99th percentile upper reference limit (URL), and with at
AMI patients, and their diagnostic value were explored. least one of the following: (a) lasting ischemic chest pain for at least
of 30 min; (b) new or presumed new significant ST segment–T wave
(ST‐T) changes or new left bundle branch block; (c) development of
2 | MATERIALS AND METHODS pathological Q waves in the electrocardiogram (ECG); (d) imaging
evidence of new loss of viable myocardium or new regional wall
2.1 | Ethical approval of the study protocol motion abnormality; (e) identification of an intracoronary thrombus
The study protocol was approved by the Qingdao University Medical by angiography. Control group were composed of healthy individuals
College committee. who without any acute dynamic ECG changes and/or rise of cardiac
enzymes, and they were matched by age, sex, and area of residence
with the patients.
2.2 | Participants Patients were excluded if they had known history of previous
Between February 2016 and December 2017, 66 AMI patients and 70 myocardial infarction, heart failure or arrhythmia, history of PCI or
healthy comparisons were presented to the Affiliated Hospital of coronary artery bypass graft surgery, chronic renal failure, liver
Qingdao University (Qingdao, China) and the Affiliated Cardiovascular disorders, and patients died within the first 48 hr.
Hospital of Qingdao University (Qingdao, China). The clinical character-
istics of the study population are summarized in Table 1. Moreover, we
2.4 | Samples collection and storage
collected blood samples before and after percutaneous coronary
intervention (PCI) to investigate the miRNA changes during the therapy. Whole blood were obtained from study subjects within 4 hr of
onset of clinical symptoms (chest pain and/or dyspnea), and 1 hr
after PCI. All blood samples (5–10 ml) were collected with
2.3 | Inclusion and exclusion criteria
K2‐EDTA‐coated tubes. Samples were centrifuged (3,000g for
The inclusion criteria for AMI patients were based on the 2012 ESC/ 10 min at 4°C), then the plasma was extracted, aliquoted,
AHA/ACC guidelines (Thygesen et al., 2012). Briefly, the inclusion transferred to RNase/DNase‐free tubes, and stored at −80°C for
criteria for patients with AMI were as follows: All of the AMI patients the following experiments.
WANG ET AL.
2.5 | Total RNA isolation
Total RNA was extracted from the plasma samples using Trizol LS
reagent (Invitrogen, Carlsbad, CA). In brief, each plasma sample
(250 μl) was mixed well with 750 μl trizol reagents in a tube. Then 3 μl
cel‐miR‐39 was added as the normalization control (Huang et al.,
2014). After chloroform (250 μl) was added and shaken vigorously by
hand for 15 s, the mixture was centrifuged at 12,000g for 10 min at
4°C. Then the supernatant was transferred to a new tube, and an
equal volume of isopropanol was added to the aqueous phase. After
mixing and incubation at room temperature for 10 min, samples were
again centrifuged for 10 min. After removal of the supernatant, the
pellet was washed with 1 ml of 75% ethanol for the initial
homogenization. Then, the sample was centrifuged for 5 min. The
RNA pellet was dissolved in diethyl pyrocarbonate water at last. The
RNA quality was measured by Nano‐Drop ND‐8000 (Thermo Fisher
Scientific, Waltham, MA).
2.6 | Real‐time quantitative reverse transcription
polymerase chain reaction (RT‐PCR) analyses
Total miRNAs was reverse‐transcribed to cDNA using Mir‐X™
miRNA First Strand Synthesis Kit (Code No. 638315; TaKaRa,
Beijing, China). The primer sequences of miRNAs were listed in
Supporting Information Table S1. The PCR amplification protocol was
30 s at 94°C, followed by 40 cycles at 94°C for 5 s and 60°C for 30 s.
Each sample analysis was carried out with three replicates. The
expression level of the target gene was normalized to that of
F I G U R E 1 The expression of microRNA in plasma from AMI patients and the control subjects. (a) miR‐19b‐3p; (b) miR‐22‐5p;
(c) miR‐122‐5p; (d) miR‐134‐5p; (e) miR‐186‐5p; (f) miR‐375. AMI: acute myocardial infarction; con: control
| 3
cel‐miR‐39. The fold change of target genes was analyzed by the
2−ΔΔCt method (Livak & Schmittgen, 2001).
2.7 | Statistical analyses
All data were represented as the mean ± standard error (SE). For
normally distributed values, Student’s two‐sided t test or one‐way
ANOVA followed by Bonferroni’s multiple comparison test as a post
hoc analysis were performed. In addition, the expression of the
miRNAs were analyzed using the repeated‐measures ANOVA
method. We performed correlation analysis of the miRNAs using
Pearson’s correlation coefficient. Receiver operating characteristic
(ROC) curves and the area under the ROC curves (AUC) were
determined to discriminate AMI patients from healthy comparisons
and to assess the diagnostic accuracy of the selected miRNAs,
respectively. SPSS 16.0 software (SPSS, Chicago, IL) was used to
perform the statistical analyses, all statistical tests were two‐tailed,
and p < 0.05 was considered statistically significant.
3 | RESULTS
3.1 | Clinical characteristics of the study
population
The baseline characteristics of the AMI patients and control
participants in this study are listed in Table 1. The median age was
61.9 years in the healthy comparisons, and 61.84 years in the AMI
4 | WANG ET AL.

group. There were no significant differences in the status of 3.2.1 | Detection of cardiac‐specific microRNAs in
hypertension, diabetes, smoking status in the AMI, and non‐AMI plasma of healthy people and patients with spinal
group. The results showed that there were no statistical differences cord injury
between the healthy comparisons and AMI patients in clinical
To confirm the specificity expressions in heart of these miRNAs, we
variables, such as white blood cell, systolic blood pressure, diastolic
detected the expression of the six microRNAs in plasma of healthy
blood pressure, total cholesterol, total triglyceride, high‐density
people and patients with spinal cord injury (P‐SCI). Result showed
lipoprotein, low‐density lipoprotein, and creatinine. Whereas
that no significant change was detected between healthy people and
CK‐MB was markedly upregulated in the AMI patients compared
P‐SCI, except miR‐375. MiR‐375, which showed significant increase
with the control subjects. In addition, the heart rate was significantly
of gene expression in P‐SCI group, indicating the low specificity for
downregulated in the AMI group compared with the control group.
AMI (Figure 2).

3.2 | The expression patterns of circulating 3.2.2 | The change of the selected miRNAs
miRNAs expression in AMI and after PCI
We used qRT‐PCR assays to investigate the expression of the selected A total of 27 cases were obtained to detect the change of the six
circulating miRNAs (miR‐19b‐3p, miR‐22‐5p, miR‐122‐5p, miR‐134‐5p, miRNAs in the pre‐PCI and post‐PCI plasma of AMI patients.
miR‐186‐5p, and miR‐375). The expression levels of all circulating Compared with the preoperative expression, three miRNAs
miRNAs for AMI were listed in Supporting Information Table S2. As demonstrated a significant change as shown in Figure 3.
shown in Figure 1, we found that the expression of miR‐22‐5p was Before PCI, the expression of miR‐22 was 0.17 ± 0.01, which
significantly decreased in the AMI group (mean ± SE: 0.17 ± 0.01; had a significant difference compared with control group
p < 0.001) compared with non‐AMI cases (mean ± SE: 1.01 ± 0.04). (p < 0.0001), while the postoperative level is 0.29 ± 0.07, which
In addition, miR‐122‐5p was significantly increased in AMI group also had a significant difference (p < 0.0001). The level of miR‐
(mean ± SE: 1.80 ± 0.29; p = 0.0451). However, no significant 122 changed from significantly increased 1.80 ± 0.29 (p = 0.0451)
difference were detected about miR‐19‐3p (mean ± SE: 0.69 ± 0.20; to no significantly changed 0.81 ± 0.42 (p = 0.5308). The expres-
p = 0.3941), miR‐134‐5p (mean ± SE: 0.82 ± 0.26; p = 0.5295), sion of miR‐375 had not significantly changed in pre‐PCI, but
miR‐186‐5p (mean ± SE: 1.46 ± 0.52; p = 0.6708), and miR‐375 (mean ± significantly decreased in post‐PCI (mean ± SE: 0.21 ± 0.07;
SE: 0.77 ± 0.08; p = 0.0687) in the AMI group. p = 0.0005).

F I G U R E 2 The expression of circulating (a) miR‐19b‐3p; (b) miR‐22‐5p; (c) miR‐122‐5p; (d) miR‐134‐5p; (e) miR‐186‐5p; (f) miR‐375 in
plasma of healthy people and patients with spinal cord injury. P‐SCI: patients with spinal cord injury
WANG ET AL. | 5

F I G U R E 3 The expression of circulating (a) miR‐19b‐3p; (b) miR‐22‐5p; (c) miR‐122‐5p; (d) miR‐134‐5p; (e) miR‐186‐5p; (f) miR‐375 in the
presurgery and postsurgery plasma of AMI patients. AMI: acute myocardial infarction; con: control

3.3 | The correlation between CK‐MB, HsTNT, and correlation with each other. And the same appeared in miR‐22‐5p,
circulating miRNAs miR‐122‐5p, and miR‐375 ( Supporting Information Table S3).

We investigated the relationship between CK‐MB, HsTNT, and

plasma miRNAs (n = 15). The results indicated that two circulating
miRNAs, miR‐22‐5p (R = 0.5216) and miR‐122‐5p (R = 0.6296),
exhibited a significantly positive correlation with HsTNT and
CK‐MB, respectively (Figure 4).
3.4 | The correlation between circulating miRNAs
We further investigated the relationship within plasma miRNAs. The
results indicated that three circulating miRNAs, miR‐19b‐3p,
miR‐134‐5p, and miR‐186‐5p, exhibited a significantly positive
3.5 | The diagnostic specificity and sensitivity of
miRNAs in AMI
To further explore the applicability of using circulating miRNAs as
potential diagnostic biomarkers for AMI, we performed ROC
analysis. The results of the ROC curve analysis indicated that
miR‐22‐5p showed a moderate power for differentiating AMI
patients from control subjects (Figure 5). The AUC was 0.975
(Supporting Information Table S4). Moreover, the composited‐
miRNAs (miR‐22‐5p and miR‐122‐5p) showed higher AUC values
(0.976) than the single miRNAs at all times course (Figure 6).

F I G U R E 4 The kinetic expressions of CK‐MB, HsTNT, and circulating miRNAs in AMI patients. AMI: acute myocardial infarction; CK‐MB:
creatine kinase; HsTNT: high‐sensitivity troponin; miRNA: microRNA [Color figure can be viewed at wileyonlinelibrary.com]
6 |
F I G U R E 5 Receiver operating characteristic curves for the diagnostic accuracy for the six miRNAs. (a) miR‐19b‐5p, (b) miR‐22‐5p, (c) miR‐122‐5p,
(d) miR‐134‐5p, (e) miR‐186‐5p, and (f) miR‐375. AUC: area under the curve [Color figure can be viewed at wileyonlinelibrary.com]
4 | D IS C U S S IO N
In the current study, we analyzed the levels of six selected miRNAs in
the plasma samples of AMI patients for their potential as diagnostic
biomarkers. The results showed that the expression levels of
circulating miR‐22‐5p were significantly downregulated in the AMI
patients’ plasma with a fold regulation of 0.17, while miR‐122‐5p
were significantly upregulated with a fold regulation of 1.80.
Moreover, the expression of these two miRNAs in healthy people
F I G U R E 6 Receive operating characteristic (ROC) curves
analyzed for the diagnostic value of circulating miRNAs. ROC curve
for plasma miR‐22 and miR‐122 and the combination of the three
miRNAs were able to distinguish AMI from the control group.
AMI: acute myocardial infarction; miRNAs: microRNAs [Color figure
can be viewed at wileyonlinelibrary.com]
WANG ET AL.
have not significantly changed compared with spinal cord injury
patients, suggesting that miR‐22‐5p and miR‐122‐5p were cardiac‐
specific microRNAs. The results before and after PCI showed that
miR‐22‐5p and miR‐122‐5p had a certain degree of recovery. There
was no significant difference in the level of miR‐122‐5p expression
after PCI compared with the control group, indicating the higher
sensitivity of miR‐122‐5p than miR‐22‐5p. Correlation analysis
showed that miR‐22‐5p was significantly positively correlated with
miR‐122‐5p. MiR‐122‐5p was positively correlated with CK‐MB,
while MiR‐22‐5p was positively correlated with HsTNT. By perform-
ing ROC curve analysis, we demonstrated that circulating miR‐22‐5p
and miR‐122‐5p had the highest discriminative value for the
diagnosis of AMI patients from controls among these six miRNAs.
Circulating miRNAs regulate gene expression at the posttranscrip-
tional level, then resulting in the termination of protein synthesis
(Suzuki & Miyazono, 2010; Urbich, Kuehbacher, & Dimmeler, 2008;
Zhao, Samal, & Srivastava, 2005). Nowadays, numerous circulating
miRNAs have been explored as novel candidate biomarkers for various
cardiovascular diseases. Marked changes of miR‐1, miR‐133, miR‐208,
and miR‐499 have been reported in AMI patients (D’Alessandra et al.,
2010; Sayed, Xia, Yang, & Peng, 2013; Wang et al., 2010), and are
considered as potential biomarkers in AMI. But the diagnostic values
are inconsistent in different studies (Pleister, Selemon, Elton, & Elton,
2013). Therefore, it is necessary to search for novel miRNAs as
indicator of AMI. Recently published studies showed that miRNAs could
regulated cell apoptosis, autophagy, and necrosis. MiR‐22 is one of the
WANG ET AL.
most abundant miRNA in the heart, which play important roles in
oxidative stress, cardiac apoptosis, autophagy, hypertrophy, fibrosis, and
regeneration (Huang & Wang, 2014; Huang et al., 2013; Small & Olson,
2011). MiR‐22 functions as an integrator of Ca2+ homeostasis and
myofibrillar protein content during stress in the heart (Gurha et al.,
2012). It is thought to be required for normal cardiac remodeling in
response to stresses (Huang & Wang, 2014). The expression of heart
miR‐22 is modestly increased when cells are stimulated by different
stimuli, then the increased expression of miR‐22 in hearts lead to the
elevated circulating miR‐22 in plasma (Gurha et al., 2012; Tu et al.,
2014; Xu et al., 2012). MiR‐122‐5p is the most abundantly expressed
miRNA in the liver, but it could be important in assessing the severity of
AMI. MiR‐122‐5p regulates apoptosis by targeting proapoptotic factors‐
related pathways (Sun et al., 2017), and has a proapoptotic effect in
H9C2 myocytes (Huang et al., 2012). More recently, overexpression of
miR‐122‐5p was confirmed in the cardiac tissue of patients who died
from AMI (Boštjančič et al., 2012; Cortez‐Dias et al., 2016). Based on
these researches above, circulating miR‐22‐5p and miR‐122‐5p could be
considered promising novel diagnostic biomarkers for AMI. Their
changing characteristics are also one of the molecular mechanisms for
in‐depth study of AMI occurrence and prediction.
The selection of the miRNAs for the current investigation was based
on previous studies, but the results are not consistent with previously
studies. MiR‐19b, miR‐134, and miR‐186 had previously been reported
associated with AMI. The expressions of these three miRNAs in this
experiment are not consistent with previously studies (Chen et al.,
2008; Gilad et al., 2008; Wang et al., 2016). In the current study, miR‐
19b, miR‐134, and miR‐186 showed no significant change in the plasma
of AMI patients, indicating the three miRNAs were also interfered by
many other factors. Such as miR‐19, an important regulator in heart
function, had critical roles in cancer development and progression (Sun,
Liu, Hong, Zhang, & Zhang, 2018; Wang et al., 2016). MiRNA‐134 was
expressed in the brain and had been demonstrated to negatively
regulate memory and plasticity (Gao et al., 2010), and miR‐186 is a
potent regulator in neuronal cells (Kim et al., 2016). MiR‐375 is a
candidate tumor suppressor miRNA in gastric carcinoma (Tsukamoto
et al., 2010), and is also highly expressed in other patients’ plasma. To
the best of our knowledge, the contributions of miRNAs in the process
of AMI are still lacking. Therefore, further studies would be necessary to
investigate miRNAs involved in AMI.
MiR‐22‐5p and miR‐122‐5p as biomarkers of AMI may offer a
number of advantages. First, miRNAs can be easily detected in whole
blood, plasma, and serum; it is more stable than protein markers in
circulation. Secondly, miR‐22‐5p and miR‐122‐5p can be detected in
a quantitative manner by real‐time PCR. Finally, the changes of
miR‐22‐5p and miR‐122‐5p in the bloodstream may reflect the
alterations of cardiac function.
5 | L I MI T AT I O N S O F O U R S TU D Y
Some limitations have to be resolved before the miRNAs actually be
applied into clinical practice. First of all, the current study is based on a
| 7
relatively small sample population analysis, and larger clinical studies
will be needed in the future to confirm the diagnostic value of these
miRNAs. Therefore, in the next phase of our studies, the sample size will
be expanded and follow‐up examinations of the patients will be
performed. Moreover, we will characterize the expression of these
miRNAs in AMI model animals, and investigate their functions and
underlying mechanisms. Such studies should explain the reason for their
changes in the blood. Secondly, levels of plasma miRNAs in different
stages of AMI have not been evaluated. In addition, the time and cost
involved in measuring circulating miRNAs should be considered before
clinical management. Therefore, the diagnostic value needs more
extensive screening and a careful identification study. The development
of highly sensitive, fast, and specific methods of ultra‐low levels of
miRNA in blood samples is critical for the clinical application as
biomarkers for AMI diagnosis and prognosis.
6 | CO NCL USION
In this study, we identified plasma miR‐22‐5p and miR‐122‐5p were
significantly increased in the AMI cases. By ROC analyses, we found
that the combination of miR‐22‐5p and miR‐122‐5p may be
promising predictors of AMI.
AC KNO WL EDG M EN TS
The study is financially supported by National Natural Science
Foundation of China (Nos. 81741173 and 81700704).
CON F LI CTS OF I NTERE ST
The authors declare that there are no conflicts of interest.
ORCI D
Yu Wang http://orcid.org/0000-0002-2274-9317
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S U P P O R T I N G I N F O RMA T I O N
Additional supporting information may be found online in the
Supporting Information section at the end of the article.
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How to cite this article: Wang Y, Chang W, Zhang Y, et al.
Circulating miR‐22‐5p and miR‐122‐5p are promising novel
biomarkers for diagnosis of acute myocardial infarction. J Cell
Physiol. 2018;1–9. https://doi.org/10.1002/jcp.27274