Supplementary Table 1. Patients characteristics cohort 1

Variable / No diabetes / Type 2 diabetes / p
n / 25 / 22
Sex, %males / 76% / 91% / 0.253
Age, years / 74.0 (67.0-77.0) / 71.0 (58.8-77.0) / 0.631
BMI, kg/m2 / 27.6 (25.9-30.6) / 29.6 (27.0-32.9) / 0.224
plasma glucose, mmol/l / 5.7 (5.5-6.8) / 7.4 (6.7-9.0) / <0.001
Operation type
Valve replacement
CABG
Valve replacement and CABG / 24%
60%
16% / 5%
73%
22% / 0.192
Glucose-lowering medication / 0 / 91% / <0.001
Cholesterol-lowering medication / 68% / 100% / 0.004
Blood pressure lowering medication
-Beta blockers
-ACE inhibitors / 68%
52% / 82%
82% / 0.331
0.063

Continuous variables are expressed as median (interquartile range), and p-values were calculated using a Mann Whitney U-test. Discontinuous parameters are expressed as percentages, and p-values were calculated using a Fisher test.

Supplementary Table 2. Patients characteristics cohort 2

variable / No diabetes / Type 2 diabetes / p
n / 20 / 35
Sex, %males / 75% / 80% / 0.740
Age, years / 69.0 (67.0-72.8) / 67.0 (61.0-75.0) / 0.489
BMI, kg/m2 / 26.3 (24.2-28.7) / 29.8 (27.1-29.8) / 0.011
plasma glucose, mmol/l / 5.1 (4.9-5.4) / 6.6 (5.6-8.1) / <0.001
Operation type
-Valve replacement
-Coronary artery bypass grafting / 20%
80% / 0%
100% / 0.016
Glucose-lowering medication / 0% / 80% / <0.001
Cholesterol-lowering medication / 70% / 89% / 0.144
Blood pressure lowering medication
-Beta blockers
-ACE inhibitors
-AT1 receptor antagonists / 55%
25%
25% / 66%
43%
23% / 0.565
0.248
1.000

Continuous variables are expressed as median (interquartile range), and p-values were calculated using a Mann Whitney U-test. Discontinuous parameters are expressed as percentages, and p-values were calculated using a Fisher test.

Supplementary Table 3. Overview of real-time PCR primers

Target / Accession / Forward 5’->3’ / Reverse 5’->3’
Human primers
ACE / NM_000789 / Quantitect assay: QT00032382
ACE2 / NM_021804 / Quantitect assay: QT00034055
ACTB / NM_001101 / GCCGAGGACTTTGATTGCAC / GGACTTCCTGTAACAACGCA
AGT / NM_000029 / Quantitect assay: QT00005614
AGTR1 / NM_000685 / Quantitect assay: QT00233548
CTSD / NM_001909 / Quantitect assay: QT00020391
CTSG / NM_001911 / Quantitect assay: QT00051667
RENIN / NM_000537 / Quantitect assay: QT00001848
AGTR2 / NM_000686 / Quantitect assay: QT00065758
YWHAZ / NM_003406 / TCTGGCTCCACTCAGTGTCT / CTGTGGGATGCAAGCAAAGG
Mouse primers
PPARA / NM_011144 / CTGCAGAGCAACCATCCAGAT / GCCGAAGGTCCACCATTTT
RPS18 / NM_011296 / AAATTCGAGCCCATAGAGGG / AGAGACTCATTTCTTCTTGGAT
Rat primers
ACE / NM_012544 / GCTCACCTGCTAGGGAACAT / GCCTCCGTGGCATCTATACT
ACE2 / NM_001012006 / CTTACGAGCCTCCTGTCACC / ATGCCAACCACTACCGTTCC
AGT / NM_134432 / TCTCCTCTACTACAGCAAGAGCA / CTTCTCATCCACGGGGGAGGT
AGTR1 / NM_030985 / GAGTAACCAAGCAAAGCCGT / CCAGACCCACCAATCCATCC
CMA1 / NM_013092 / GGGCCAGTGTGTGAGGAAAT / TACAGACAGGCCAGATCCCA
EEF1A1 / NM_175838 / GGGGACAATGTAGGCTTCAA / TCCATTGGTGGGTCATTTTT
HPRT1 / NM_012583 / GGTCCTTTTCACCAGCAAGCT / GGTCCTTTTCACCAGCAAGCT
RENIN / NM_012642 / CCCCCAACATAGGGACACTG / CAAAGCAGGGAAGGGTGAGT

Supplementary Table 4.Effect of miR-208a and AngII on the expression of genes involved in the regulation of fatty acid metabolism

Target / basal / miR-208a / AngII
Acaa1a / 100±2.5 / 93.7±3.7 / 145±37.9**
Acaa2 / 100±2.9 / 114±13.7 / 151±90.2
Acad10 / 100±2.4 / 94.0±5.8 / 162±48.2**
Acad11 / 100±3.0 / 89.6±1.6 / 153±30.2***
Acad9 / 100±3.4 / 117.4±7.1 / 70.2±32.3*
Acadl / 100±3.7 / 99.5±9.2 / 76.9±29.5
Acadm / 100±30.7 / 110±10.5 / 113±50.9
Acads / 100±2.5 / 90.2±6.5 / 202±77.4**
Acadsb / 100±2.5 / 87.1±3.6 / 149±67.6
Acadvl / 100±3.7 / 96.5±7.9 / 159±115
Acat1 / 100±3.5 / 92.3±4.2 / 137±23.5***
Acat2 / 100±2.7 / 114±9.3 / 70.6±35.1
Acot2 / 100±13.9 / 105±27.6 / 228±197
Acot3 / 100±4.5 / 101±10.1 / 104±32.2
Acot7 / 100±2.4 / 93.3±8.3 / 113±10.7*
Acot8 / 100±3.8 / 100±11.7 / 122±11.6**
Acot9 / 100±3.6 / 110±16.8 / 138±27.9**
Acox1 / 100±2.8 / 93.5±10.9 / 92.0±12.9
Acox2 / 100±3.2 / 142±15.9* / 46.9±39.8**
Acsbg1 / 100±2.1 / 77.8±19.2 / 139.2±147.1
Acsl1 / 100±3.2 / 115±11.8 / 54.7±35.5**
Acsl3 / 100±1.3 / 122±11.3 / 91.2±39.2
Acsl4 / 100±1.3 / 109±10.5 / 87.4±28.1
Acsl5 / 100±2.7 / 106±8.3 / 154±73.4
Acsl6 / 100±2.2 / 157±8.9*** / 91.7±33.6
Acsm3 / 100±2.6 / 102±18.6 / 83.5±85.0
Acsm4 / 100±3.2 / 104±20.9 / 221±112**
Aldh2 / 100±3.2 / 175±18.9*** / 72.9±7.9*
Bdh1 / 100±1.8 / 107±15.0 / 97.2±36.3
Bdh2 / 100±3.4 / 115±15.4 / 56.5±30.1**
Cpt1a / 100±3.4 / 96.7±17.6 / 151±75.8
Cpt1b / 100±2.9 / 100±2.9 / 439±236***
Cpt1c / 100±2.1 / 76.9±10.1*** / 73.0±9.7***
Cpt2 / 100±2.0 / 101±5.5 / 70.0±18.6***
Crat / 100±2.9 / 96.1±9.1 / 92.8±43.7
Crot / 100±2.9 / 86.1±4.4 / 141±62.3
Decr / 100±3.1 / 114±14.5 / 75.3±50.9
Echs1 / 100±2.9 / 91.4±11.8 / 118±30.4
Eci2 / 100±3.0 / 110±13.3 / 128±59.3
Ehhadh / 100±2.5 / 151±25.4* / 110±44.6
Fabp1 / 100±3.7 / 98.1±40.7 / 152±155
Fabp2 / 100±4.4 / 112±24.1 / 121±100
Fabp3 / 100±3.1 / 106±8.6 / 97.4±14.7
Fabp4 / 100±2.6 / 108±34.6 / 82.4±39.5
Fabp5 / 100±1.7 / 120±10.8 / 76.4±31.0
Gcdh / 100±2.1 / 96.6±15.4 / 197±40.7***
Gpd1 / 100±2.5 / 83.6±7.8 / 89.9±19.9
Gpd2 / 100±2.3 / 102±7.4 / 52.7±25.7***
Gusb / 100±2.2 / 95.0±11.8 / 97.7±7.4
Gyk / 100±2.2 / 99.1±14.8 / 215±103**
Hadha / 100±1.8 / 103±10.1 / 107±21.5
Hmgcl / 100±1.7 / 105±4.7 / 109±42.7
Hmgcs1 / 100±2.9 / 84.9±19.5 / 280±250
Hmgcs2 / 100±1.9 / 83.1±6.6 / 197±139
Lipe / 100±3.0 / 107±9.2 / 420±546
Lpl / 100±1.9 / 104±6.5 / 86.7±14.9*
Mccee / 100±4.1 / 118±19.2* / 77.2±3.5*
Mut / 100±3.3 / 100±1.5 / 67.3±42.1
Oxct2a / 100±2.9 / 117±25.5 / 90.8±31.5
Pecr / 100±3.0 / 115±16.3 / 72.6±15.7**
Ppa1 / 100±1.8 / 110±7.4 / 91.6±9.6
Prkaa1 / 100±4.0 / 117±12.4 / 50.8±37.1**
Prkaa2 / 100±2.9 / 98.0±8.6 / 120±63.6
Prkab1 / 100±1.5 / 90.3±11.2 / 157±71.9
Prkab2 / 100±4.4 / 141±18.4* / 54.6±31.9**
Prkaca / 100±2.5 / 100±20.8 / 181±119
Prkacb / 100±1.6 / 115±21.4 / 119±85.6
Prkag1 / 100±3.1 / 93.7±19.8 / 93.7±31.0
Prkag3 / 100±3.1 / 134±29.9 / 238±195
Slc27a3 / 100±3.0 / 105±11.2 / 193±48.7***

Values are expressed as mean ± SD (n=4 for treatment groups, n=8 for basal). Expression levels for untreated cells (basal) were set at 100%. Differences among groups were examined by ANOVA and Bonferroni correction for multiple comparisons. ***, **, and * indicate P<0.001, P<0.01, and P<0.05 for differences versus basal.

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