SUPPLEMENTARY MATERIAL
Detailed methods
Study design
Diabetes was induced in 4-month old male C57/B6 mice by a single high dose of streptozotocin
(STZ, 180 mg/Kg, via intraperitoneal injection), dissolved in sterile 0.025 M citrate buffer (pH 4.5)
and injected within 10 minutes. An equal volume of citrate buffer was administered in control
animals. Hyperglycemia was defined as 3 random blood glucose levels >13.9 mmol/l following STZ
injection. Mice were housed in temperature-controlled cages (20–22°C), fed ad libitum, and
maintained on a 12:12-h light/dark cycle. Animal experiments were conducted in accordance with
the guidelines approved by the Institutional Animal Care Committee (Kommission für Tierversuche
des Kantons Zürich, Switzerland). Three experimental groups were studied: 1) controls, 2) diabetic
mice, and 3) diabetic mice undergoing intensive glycemic control by insulin. Treatment with insulin
commenced 3 weeks after the induction of diabetes and was maintained for the following 3 weeks.
All mice were euthanized after 6-week follow-up (Figure S1).
Insulin implants
Insulin (1 implant/10 g of body weight) was administered as slow release implants placed
subcutaneously under the mid dorsal skin (LinBit, LinShin, Canada) after anaesthesia with
isofluorane (FORENE, Baxter Healthcare Corporation, USA). Glycemic control was assessed by
measuring blood glucose form the tail vein with a spin-in sampling glucose meter (Glucometer Elite
XL, Bayer, Laubach, Germany, Figure S2). Groups 1 and 2 received placebo instead of insulin
(micro-recrystallized Palmitic acid, LinShin, Canada).
Tissue harvesting
Mice were euthanized by intraperitoneal administration of sodium pentobarbital. The chest cavity
was opened by making an incision in the diaphragm and the heart harvested by cutting the great
vessels. After harvesting, the organ was placed immediately in ice cold PBS, cleaned and snapfrozen in liquid nitrogen. Left ventricular specimens were used for miRNA expression.
miRNA Expression Profiling Workflow
Profiling of miRNAs in heart samples from the 3 experimental groups was performed by Mouse
miRNome miRNA PCR Array (SABioscence, Frederick, MD, USA). Total RNA was isolated from
heart specimens collected from controls and diabetic mice with or without insulin treatment using
the miRNeasy Mini Kit (Qiagen, Hilden, Germany). cDNA was then prepared from each total RNA
(500 ng) in a miScript II reverse transcription reaction using HiSpec Buffer (Qiagen, Hilden,
Germany) and used for Mouse miRNome miRNA PCR Array. Real-time PCR amplification was
performed in a MX3000P PCR cycler (Stratagene) using miScript SYBR Green PCR Kit (Qiagen,
Hilden, Germany). The amplification program consisted of 1 cycle at 95 °C for 15 min, followed by
40 cycles with a denaturing phase at 94 °C for 15 s, an annealing phase at 55 °C for 30 s, and an
elongation phase at 72 °C for 30 s. Data analysis was performed using the online miScript miRNA
PCR Array data analysis tool. Each array was performed from three independent experiments.
Raw data of the mouse miRNome are reported in Tables S1 and S2.
Ingenuity pathway analysis
The lists of miRNAs, differentially expressed in each experimental group (with p < 0.05), were
uploaded in the IPA tool (Ingenuity® Systems,www.ingenuity.com) and analysed on the basis of
IPA library of canonical pathways. The significance of the association between each list and a
canonical pathway was measured by Fisher’s exact test. As a result, a p value was obtained,
determining the probability that the association between miRNAs in our data set and a canonical
pathway can be explained by chance alone. IPA-derived pathways of myocardial damage are
reported in Table S3.
Statistical analysis
Statistical analysis for miRNA arrays was performed using GraphPad Prism Software (version 5.0).
Comparisons were made by using the Student t test for unpaired data and 1-way ANOVA, followed
by Bonferroni’s post-hoc test, when appropriate. Probability values less than 0.05 were considered
statistically significant.
SUPPLEMENTARY FIGURES
Figure S1. Study design.
Figure S2. Graph showing achievement of an optimal glycemic control in diabetic mice treated
with insulin from week to 4 to 6. Results are presented as mean±SEM; *, p<0.01 vs. control, #,
p<0.01 vs diabetes. Wk, week.
SUPPLEMENTARY TABLES
Table S1. Persistently upregulated miRNAs despite insulin treatment. A two-fold change (FC) and
p value <0.05 were considered to indicate significant miRNAs variations. Raw and adjusted p
values refer to 1-way ANOVA and Bonferroni’s post-hoc test, respectively.
p value
Diabetes vs
Control (FC)
Raw
hsa-miR-618
48.75
hsa-miR548b-3p
p value
Adjusted
Insulin vs
Control (FC)
Raw
Adjusted
0.0042
0.013
46.13
0.0055
0.017
44.74
0.0025
0.0074
43.69
0.0028
0.0084
hsa-miR-372
38.92
0.0036
0.011
35.26
0.0059
0.018
hsa-miR-379
36.79
0.0007
0.0020
32.96
0.0012
0.0037
hsa-miR-187
31.09
0.0001
0.0004
30.37
0.0002
0.0005
hsa-miR-744
30.44
0.0085
0.026
28.38
0.012
0.035
hsa-miR-99b
26.54
0.0016
0.0048
22.41
0.0038
0.012
hsa-miR-564
26.04
0.0004
0.0013
21.85
0.0011
0.0034
25.65
0.0044
0.013
26.75
0.0036
0.011
21.01
0.0039
0.012
23.17
0.0024
0.0071
19.86
0.011
0.033
19.68
0.012
0.035
18.73
0.015
0.045
23.56
0.0052
0.016
19.62
0.0015
0.0046
15.40
0.0054
0.016
18.51
0.0093
0.028
20.57
0.0056
0.017
15.64
0.0004
0.0012
17.03
0.0002
0.0007
15.10
<0.0001
0.0002
13.20
0.0002
0.0005
hsa-miR-217
14.04
0.0010
0.0031
13.08
0.0015
0.0046
hsa-miR-630
13.07
0.0017
0.0050
12.60
0.0021
0.0062
hsa-miR548j
12.35
0.013
0.039
16.86
0.0028
0.0084
hsa-miR-622
12.29
0.0050
0.0150
13.62
0.0029
0.0087
miRNA
hsa-miR520d-3p
hsa-miR1305
hsa-miR-18a
hsa-miR455-5p
hsa-miR518f
hsa-miR-182
hsa-miR337-5p
hsa-miR190b
hsa-miR129-3p
hsa-miR139-5p
hsa-miR502-3p
hsa-miR103b
12.26
0.0008
0.0025
14.60
0.0003
0.0009
11.94
0.015
0.046
14.54
0.0059
0.018
11.64
0.0004
0.0011
12.48
0.0002
0.0007
11.46
0.0005
0.0014
9.08
0.0018
0.0054
11.10
<0.0001
<0.0001
12.91
<0.0001
<0.0001
10.82
0.0061
0.018
9.61
0.011
0.033
10.33
0.0002
0.0007
8.99
0.0005
0.0016
10.33
0.0003
0.0008
9.39
0.0005
0.0015
10.21
0.0004
0.0011
8.76
0.0009
0.0026
10.12
0.0002
0.0006
10.90
0.0001
0.0004
10.04
0.0022
0.0065
11.86
0.0008
0.0025
9.99
0.011
0.032
12.56
0.0033
0.010
9.80
0.0005
0.0014
10.40
0.0003
0.0010
9.75
0.0042
0.012
8.00
0.012
0.035
9.69
0.0001
0.0003
6.62
0.0012
0.0035
9.65
0.0010
0.0029
9.00
0.0014
0.0043
hsa-miR-215
9.09
<0.0001
<0.0001
8.51
<0.0001
<0.0001
hsa-miR-380
9.06
0.0019
0.0058
10.62
0.0008
0.0023
hsa-miR3130-5p
8.97
0.0039
0.012
6.72
0.017
0.050
hsa-miR-580
8.90
0.0007
0.0021
8.78
0.0008
0.0023
hsa-miR-298
8.76
<0.0001
0.0003
9.70
<0.0001
0.0001
8.50
0.0008
0.0023
6.23
0.0048
0.014
8.32
0.0020
0.0059
8.89
0.0013
0.0040
8.17
0.0002
0.0005
7.27
0.0004
0.0011
7.63
0.0018
0.0054
6.68
0.0039
0.012
hsa-miR-514
7.54
0.0052
0.016
6.90
0.0083
0.025
hsa-miR1278
7.54
0.0087
0.026
7.48
0.0091
0.027
hsa-miR-224
hsa-miR525-3p
hsa-miR3917
hsa-miR-218
hsa-miR216a
hsa-miR324-3p
hsa-miR3151
hsa-miR-25*
hsa-miR490-3p
hsa-miR501-5p
hsa-miR4315
hsa-miR301a
hsa-miR4317
hsa-miR-283p
hsa-miR1251
hsa-miR216b
hsa-miR-19b
7.48
<0.0001
<0.0001
9.52
<0.0001
<0.0001
hsa-miR3907
7.30
0.0003
0.0009
9.65
<0.0001
0.0002
hsa-let-7a
7.21
0.0014
0.041
7.94
0.0084
0.025
hsa-miR3616-3p
7.20
<0.0001
0.0001
7.56
<0.0001
0.0001
hsa-miR-329
7.18
0.0005
0.0014
7.34
0.0004
0.0012
hsa-miR1284
7.10
0.0003
0.0005
6.91
0.0003
0.0009
hsa-miR-639
7.03
<0.0001
0.0003
7.63
<0.0001
0.0002
hsa-miR-221
6.95
0.0001
0.0003
5.53
0.0002
0.0005
6.92
0.0064
0.019
6.89
0.0066
0.020
6.82
<0.0001
<0.0001
5.20
<0.0001
0.0002
6.67
0.0007
0.0022
7.40
0.0004
0.0012
6.64
0.0010
0.0029
4.34
0.012
0.036
6.60
<0.0001
<0.0001
5.72
<0.0001
0.0002
6.52
0.0038
0.011
7.99
0.0011
0.0034
hsa-miR-612
6.48
0.0055
0.017
6.82
0.0041
0.012
hsa-miR-326
6.43
0.0001
0.0003
5.28
0.0004
0.0013
hsa-miR1280
6.34
0.0018
0.0053
5.36
0.0048
0.014
hsa-miR-137
6.27
0.0055
0.016
6.51
0.0044
0.013
hsa-miR-941
6.07
0.0017
0.0052
5.46
0.0033
0.0098
6.00
<0.0001
0.0002
6.47
<0.0001
0.0001
5.99
0.0013
0.0038
6.61
0.0007
0.0020
5.97
<0.0001
<0.0001
6.78
<0.0001
<0.0001
hsa-miR-34a
5.87
<0.0001
<0.0001
5.27
<0.0001
<0.0001
hsa-miR-578
5.71
0.0007
0.0022
3.80
0.0094
0.028
hsa-miR520a-3p
5.66
<0.0001
0.0001
3.54
0.0010
0.0031
hsa-miR-873
5.66
0.0006
0.0018
4.45
0.0028
0.0085
hsa-miR526b*
5.59
0.0001
0.0003
4.79
0.0003
0.0010
hsa-miR513a-3p
hsa-miR628-5p
hsa-miR129-5p
hsa-miR144*
hsa-miR628-3p
hsa-miR3145-3p
hsa-miR512-5p
hsa-miR4252
hsa-miR548c-3p
hsa-miR876-3p
5.55
0.016
0.048
5.61
0.015
0.045
hsa-miR-629
5.35
0.0005
0.0015
5.88
0.0003
0.0008
hsa-miR-597
5.34
0.0009
0.0027
4.54
0.0025
0.0075
hsa-miR3916
5.31
0.0007
0.0022
4.79
0.0014
0.0042
hsa-miR-152
5.29
0.0014
0.0043
4.25
0.0056
0.017
hsa-miR-27a
5.27
0.012
0.037
5.97
0.0062
0.019
5.17
0.0094
0.028
5.27
0.0084
0.025
5.13
0.0018
0.0054
4.86
0.0025
0.0075
hsa-miR-596
5.08
0.0029
0.0088
4.54
0.0058
0.017
hsa-miR-920
5.07
0.0026
0.0078
4.29
0.0072
0.022
5.07
0.0007
0.0022
4.87
0.0010
0.0029
5.02
0.0017
0.0050
3.47
0.016
0.048
4.99
0.0013
0.0040
6.29
0.0003
0.0009
4.97
0.0014
0.0042
3.65
0.0097
0.029
4.87
<0.0001
<0.0001
6.82
<0.0001
<0.0001
4.75
0.0005
0.0015
5.26
0.0002
0.0005
4.74
0.013
0.039
4.51
0.017
0.050
4.74
0.0044
0.013
4.36
0.0072
0.022
hsa-miR-375
4.63
0.0010
0.0029
4.46
0.0006
0.0018
hsa-miR-553
4.60
0.0016
0.0048
4.01
0.0039
0.012
hsa-miR4293
4.54
0.0041
0.012
4.07
0.0049
0.024
hsa-miR-192
4.54
0.0016
0.0049
3.38
0.0023
0.0069
hsa-miR-608
4.51
0.0067
0.020
5.31
0.0025
0.0075
4.49
0.0006
0.0019
4.17
0.0011
0.0032
4.49
<0.0001
<0.0001
4.17
<0.0001
<0.0001
hsa-miR-18b
4.49
0.0034
0.010
3.58
0.014
0.041
hsa-miR450b-3p
4.44
0.0001
<0.0001
5.17
<0.0001
<0.0001
hsa-miR1185
hsa-miR183*
hsa-miR299-3p
hsa-miR125a-3p
hsa-miR361-5p
hsa-miR1299
hsa-miR892b
hsa-miR-641
hsa-miR3141
hsa-miR1265
hsa-miR4257
hsa-miR3122
hsa-miR1207-5p
hsa-miR1257
hsa-miR363*
hsa-miR146a
4.41
0.012
0.037
5.62
0.0031
0.0092
4.41
0.0031
0.0094
4.50
0.0028
0.0083
4.41
0.012
0.037
3.32
0.0042
0.013
4.39
0.010
0.031
4.04
0.016
0.048
hsa-miR-378
4.38
0.0054
0.016
4.42
0.0051
0.015
hsa-miR199a-3p
4.38
0.015
0.046
4.34
0.016
0.049
hsa-miR-381
4.37
0.0011
0.0033
3.25
0.0080
0.024
hsa-miR-190
4.35
0.0033
0.010
4.01
0.0055
0.016
4.34
0.0013
0.0038
5.58
0.0002
0.0007
4.30
0.0006
0.0017
4.97
0.0002
0.0006
hsa-miR-504
4.30
0.0026
0.0078
3.54
0.0090
0.027
hsa-miR3670
4.25
<0.0001
<0.0001
3.73
<0.0001
<0.0001
hsa-miR-633
4.25
0.0060
0.018
5.12
0.0019
0.0057
hsa-miR-33b
4.24
0.0026
0.0078
3.26
0.014
0.041
4.20
0.0001
0.0003
5.53
<0.0001
<0.0001
4.19
0.0009
0.0028
3.93
0.0014
0.0041
4.19
<0.0001
0.0002
2.46
0.0037
0.011
4.12
0.0051
0.015
3.66
0.010
0.031
4.11
0.0020
0.0059
4.34
0.0014
0.0041
4.05
0.0022
0.0066
4.75
0.0008
0.0023
4.04
0.0081
0.0243
4.84
0.0027
0.008
4.02
0.0020
0.0060
3.85
0.0026
0.0079
4.01
0.0018
0.0053
2.85
0.0170
0.05
4.00
0.0001
0.0003
2.82
0.0015
0.0046
3.93
<0.0001
0.0001
2.73
0.0007
0.0020
3.84
<0.0001
0.0001
3.89
<0.0001
<0.0001
3.82
0.0046
0.014
3.14
0.0044
0.013
hsa-miR2114
hsa-miR3925-5p
hsa-miR1306
hsa-miR1288
hsa-miR1269
hsa-miR1183
hsa-miR-212
hsa-miR1233
hsa-miR582-5p
hsa-miR499-5p
hsa-miR181c
hsa-miR1304
hsa-miR3158-3p
hsa-miR26a-1*
hsa-miR330-3p
hsa-miR330-5p
3.76
0.0047
0.014
3.39
0.0091
0.027
hsa-miR-563
3.76
0.017
0.05
3.98
0.013
0.039
hsa-miR-451
3.75
0.016
0.047
3.89
0.013
0.038
3.74
0.012
0.036
4.73
0.0029
0.0087
3.73
0.0025
0.0076
3.43
0.0045
0.013
3.72
0.019
0.050
4.11
0.011
0.033
3.70
0.0008
0.0025
2.77
0.0067
0.020
3.61
0.0031
0.0094
3.66
0.0029
0.0086
3.59
0.0008
0.0024
4.11
0.0003
0.0009
3.51
0.0066
0.020
4.14
0.0023
0.0068
3.49
0.0067
0.020
3.38
0.0082
0.025
3.37
0.0030
0.0089
3.13
0.0049
0.015
3.34
0.0002
0.0005
2.76
0.0008
0.0024
3.29
0.0027
0.0080
3.78
0.0010
0.0029
3.28
<0.0001
<0.0001
2.76
<0.0001
0.0001
3.28
0.0013
0.0040
3.42
0.0010
0.0030
3.27
0.012
0.037
3.92
0.0040
0.012
3.27
0.0037
0.011
3.12
0.0052
0.016
3.19
0.010
0.031
3.99
0.0027
0.0082
3.18
0.0008
0.0025
3.50
0.0004
0.0012
hsa-miR-549
3.18
0.0028
0.0083
4.32
0.0003
0.0009
hsa-miR-938
3.18
0.0023
0.0070
2.98
0.0038
0.011
hsa-miR-214
3.12
0.0002
0.0006
2.88
0.0004
0.0011
hsa-miR323-5p
3.11
0.0029
0.0087
3.62
0.0010
0.0029
hsa-miR-937
3.08
0.019
0.05
4.04
0.0035
0.010
3.07
0.0032
0.0096
3.03
0.0035
0.011
3.06
0.0067
0.020
3.06
0.0067
0.020
hsa-miR4262
hsa-miR3065-3p
hsa-miR1231
hsa-miR3692
hsa-miR125b
hsa-miR1537
hsa-miR3713
hsa-miR-210
hsa-miR302d
hsa-miR515-3p
hsa-miR4302
hsa-miR-147
hsa-miR422a
hsa-miR3923
hsa-miR3687
hsa-miR193a-3p
hsa-miR1909*
hsa-miR423-5p
hsa-miR1245
hsa-miR1205
hsa-miR1260b
3.01
<0.0001
<0.0001
3.82
<0.0001
<0.0001
2.98
0.0001
0.0003
3.17
<0.0001
0.0002
2.98
0.0003
0.0009
3.90
<0.0001
<0.0001
2.97
0.017
0.050
3.37
0.0087
0.026
2.95
0.0032
0.0097
3.18
0.0019
0.0056
2.93
0.0022
0.0067
3.50
0.0006
0.0018
2.92
0.0040
0.012
3.30
0.0016
0.0049
2.92
0.0015
0.0044
3.25
0.0006
0.0019
2.91
0.0077
0.023
4.59
0.0003
0.0009
2.78
0.0032
0.0096
4.17
0.0002
0.0005
2.77
0.0030
0.0089
2.94
0.0018
0.0055
2.75
0.0074
0.022
3.12
0.0030
0.0089
2.75
0.0041
0.012
3.33
0.001
0.0029
2.69
0.0005
0.0014
2.63
0.0006
0.0017
2.63
0.0068
0.021
3.06
0.0022
0.0066
2.59
0.0047
0.014
2.73
0.0032
0.0097
hsa-miR-922
2.57
<0.0001
<0.0001
2.21
<0.0001
<0.0001
hsa-miR339-5p
2.44
0.0020
0.0059
2.76
0.0007
0.0020
hsa-miR-22*
2.44
0.0089
0.027
3.26
0.0010
0.0029
2.34
0.0061
0.021
2.73
0.0020
0.0060
2.32
0.013
0.040
3.44
0.0007
0.0020
2.27
0.0001
0.0004
2.73
<0.0001
<0.0001
2.06
0.0078
0.023
2.58
0.0011
0.0033
hsa-miR-145
hsa-miR320b
hsa-miR3159
hsa-miR589*
hsa-miR3675-5p
hsa-miR509-3-5p
hsa-miR1252
hsa-miR4264
hsa-miR-888
hsa-miR3136-5p
hsa-miR767-3p
hsa-miR-662
hsa-miR3658
hsa-miR548k
hsa-miR1471
hsa-miR892a
hsa-miR1250
hsa-miR3651
Table S2. Persistently downregulated miRNAs despite insulin treatment. A two-fold change (FC)
and p value <0.05 were considered to indicate significant miRNAs variations. Raw and adjusted p
values refer to 1-way ANOVA and Bonferroni’s post-hoc test, respectively.
p value
Diabetes vs
Control (FC)
Raw
hsa-miR-3625p
-71.02
hsa-miR-765
p value
Adjusted
Insulin vs
Control (FC)
Raw
Adjusted
<0.0001
<0.0001
-68.69
<0.0001
<0.0001
-66.29
<0.0001
<0.0001
-65.53
<0.0001
<0.0001
hsa-miR-5013p
-67.59
0.0034
0.010
-61.73
0.0034
0.010
hsa-miR-374c
-47.44
<0.0001
0.0002
-50.25
<0.0001
0.0002
hsa-miR-3385p
-22.30
0.0015
0.0045
-20.89
0.0016
0.0047
hsa-miR-619
-13.40
0.0001
0.0003
-11.13
<0.0001
0.0002
hsa-miR-518b
-11.35
0.0006
0.0019
-12.09
0.0009
0.0027
hsa-miR-134
-11.22
0.0070
0.021
-10.16
0.0083
0.025
hsa-miR-1382*
-10.89
0.0006
0.0018
-11.46
0.0007
0.0021
hsa-miR-2052
-10.52
<0.0001
<0.0001
-11.92
<0.0001
<0.0001
hsa-miR519e*
-10.14
<0.0001
0.0003
-12.44
0.0002
0.0005
hsa-miR-579
-9.42
0.012
0.035
-9.23
0.0030
0.0091
hsa-miR-5083p
-8.78
0.0002
0.0005
-8.16
<0.0001
0.0003
hsa-miR-648
-8.62
0.0026
0.0079
-9.36
0.0033
0.0099
hsa-miR-96
-8.35
0.0007
0.0022
-8.82
0.0007
0.0020
hsa-miR-5245p
-8.09
0.0024
0.0071
-7.05
0.0021
0.0063
hsa-miR-548t
-8.01
0.011
0.033
-7.95
0.015
0.044
hsa-miR-200a
-7.26
0.0034
0.010
-6.61
0.0027
0.0082
hsa-miR-5095p
-7.24
0.011
0.034
-6.74
0.0078
0.023
hsa-miR-379*
-7.19
0.0006
0.0017
-7.73
0.0007
0.0020
hsa-miR-98
-7.08
<0.0001
0.0001
-6.10
<0.0001
0.0002
hsa-let-7e
-7.04
0.011
0.033
-7.27
0.0096
0.029
miRNA
hsa-miR-1279
-6.55
0.0001
0.0004
-7.38
0.0002
0.0006
hsa-miR-135a
-6.51
0.0026
0.0077
-7.76
0.0035
0.010
hsa-miR-8753p
-6.36
<0.0001
0.0002
-6.56
0.0002
0.0005
hsa-miR-34b
-6.11
<0.0001
0.0001
-6.39
<0.0001
0.0001
hsa-miR-155
-6.08
0.0003
0.0010
-8.35
0.0003
0.0008
hsa-miR146b-5p
-5.77
<0.0001
0.0001
-4.95
<0.0001
0.0002
hsa-miR-605
-5.56
0.0002
0.0007
-6.30
0.0002
0.0007
hsa-miR449b*
-5.55
0.0016
0.0049
-4.82
0.0018
0.0055
hsa-miR-3154
-5.33
0.0001
0.0003
-4.19
0.0001
0.0004
hsa-miR-223
-5.25
0.0001
0.0003
-5.21
0.0001
0.0003
hsa-miR-3613p
-5.19
<0.0001
<0.0001
-5.32
<0.0001
<0.0001
hsa-miR-4305
-5.07
0.0002
0.0007
-5.56
0.0002
0.0007
hsa-miR-148b
-5.06
0.017
0.050
-6.55
0.014
0.041
hsa-miR-2195p
-5.02
0.0093
0.028
-4.24
0.015
0.044
hsa-miR-587
-4.88
0.0017
0.0051
-4.73
0.0031
0.0094
hsa-miR514b-3p
-4.76
0.0005
0.0014
-4.62
0.0005
0.0015
hsa-miR-19a
-4.69
<0.0001
<0.0001
-5.43
<0.0001
<0.0001
hsa-miR-3611
-4.65
0.0009
0.0027
-5.17
0.0008
0.0024
hsa-miR-153
-4.55
0.0002
0.0005
-3.51
0.0004
0.0013
hsa-miR-103a
-4,41
0.013
0.039
-4,73
0.012
0.035
hsa-miR-17
hsa-miR-106a
-4.32
0.0013
0.0039
-4.84
0.0026
0.0078
hsa-miR-133a
-4.13
0.012
0.037
-4.33
0.013
0.038
hsa-miR-496
-4.18
0.017
0.050
-5.84
0.016
0.048
hsa-let-7c
-3.98
0.013
0.039
-4.26
0.0066
0.020
hsa-miR-211
-3.93
0.0057
0.017
-4.16
0.0050
0.015
hsa-miR-206
-3.87
<0.0001
0.0001
-3.52
<0.0001
0.0002
hsa-miR-466
-3.82
0.0004
0.0011
-3.96
0.0005
0.0015
hsa-miR-30a
-3.82
0.012
0.035
-4.10
0.0094
0.028
hsa-miR-658
-3.76
0.0055
0.016
-3.75
0.0056
0.017
hsa-miR-1513p
-3.66
0.0002
0.0006
-3.43
0.0002
0.0007
hsa-miR-942
-3.65
0.0099
0.030
-4.30
0.0035
0.010
hsa-miR-376c
-3.58
0.013
0.038
-3.91
0.011
0.032
hsa-miR-640
-3.57
0.0004
0.0012
-3.04
0.0009
0.0026
hsa-miR-588
-3.56
0.0027
0.0080
-4.06
0.0019
0.0057
hsa-miR-26b
-3.53
0.015
0.045
-3.55
0.015
0.045
-3.52
0.0017
0.0051
-3.12
0.0016
0.0049
-3.52
0.0001
0.0003
-4.62
<0.0001
0.0002
hsa-miR-128
-3.51
0.0063
0.019
-3.16
0.0091
0.027
hsa-miR-302a
-3.35
<0.0001
0.0002
-3.14
<0.0001
0.0003
hsa-let-7g
-3.34
<0.0001
<0.0001
-3.81
<0.0001
<0.0001
-3.21
0.016
0.049
-3.28
0.016
0.047
-3.17
0.013
0.038
-3.24
0.011
0.034
-3.17
0.0015
0.0046
-4.34
0.0007
0.0022
hsa-miR-143
-3.16
0.0015
0.0044
-2.76
0.0027
0.0080
hsa-miR-33a
-3.15
0.0019
0.0058
-4.09
0.0009
0.0026
hsa-miR-29a
-3.12
0.0018
0.0053
-3.46
0.0014
0.0043
hsa-miR-29b
-3.07
0.016
0.047
-3.32
0.015
0.046
hsa-miR-9
-3.05
<0.0001
<0.0001
-3.46
<0.0001
<0.0001
hsa-miR-15b
-3.04
0.0033
0.010
-4.04
0.0015
0.0045
hsa-miR-924
-3.00
0.0028
0.0085
-2.82
0.0053
0.016
hsa-miR-1
-2.99
0.016
0.048
-2.74
0.012
0.037
hsa-miR-506
-2.97
0.0059
0.018
-3.57
0.0075
0.022
hsa-miR-431*
-2.94
0.0004
0.0011
-2.23
0.0011
0.0032
hsa-miR-30e
-2.93
0.017
0.050
-3.58
0.012
0.037
hsa-miR-5423p
hsa-miR-1405p
hsa-miR-4093p
hsa-miR-1515p
hsa-miR-34c5p
hsa-miR-1301
-2.89
0.0033
0.010
-2.31
0.0085
0.026
hsa-miR-4277
-2.87
<0.0001
<0.0001
-3.44
<0.0001
<0.0001
hsa-miR-431
-2.87
0.0003
0.0010
-3.49
0.0002
0.0007
hsa-miR-21
-2.68
0.0002
0.0005
-2.37
0.0002
0.0006
hsa-miR-150
-2.62
0.013
0.039
-2.56
0.013
0.040
hsa-miR-425
-2,45
0.0002
0.0007
-2,59
0.0003
0.0008
hsa-miR-30b
-3.41
0.0026
0.0078
-3.27
0.0015
0.0044
hsa-miR-559
-2.74
0.0020
0.0060
-2.10
0.0055
0.016
hsa-miR-184
-2.37
0.0041
0.012
-2.56
0.0051
0.015
hsa-miR-181b
-2.32
0.0092
0.028
-2.93
0.0047
0.014
hsa-miR-320a
-2.31
0.011
0.033
-3.11
0.0076
0.023
hsa-miR-181a
-2.26
0.0011
0.0034
-2.42
0.0009
0.0027
hsa-miR-448
-2.21
0.0034
0.010
-2.50
0.0017
0.0051
hsa-miR-16
-2.17
0.0091
0.027
-3.11
0.0053
0.016
Table S3. Ingenuity Pathway Analysis showing dysregulated miRNAs involved in pathways of
myocardial damage.
Category
miRNA
p value
Apoptosis
miR-320b, miR-378, miR-34a
4.92E-02
Fibrosis
miR-125b, miR-150, miR-199a, miR-29b, miR-30a
5.60E-03
miR-1, miR-150, miR199a, miR-133a, miR-214, miR-
3.02E-02
Hypertrophy
29a, miR-125b, miR-221, miR-212
Autophagy
miR-133a, miR-221, miR-212, miR-30a
4.92E-02
miR-221, miR-146a, miR-34a, miR-210, miR-19b, miR-
2.25E-07
Oxidative stress
125b, miR-27a, miR-155
Heart Failure
miR-423, miR-499, miR-199a
1.48E-05