Introduction 1 2 3 4 5 Patients and methods Characterization of study groups 1 1 1 Table 1 Characterization of study groups Code Group Age (years) EF (%) LVEDD (mm) INFLAM PVB19 EV AdV HHV6 EBV GA-1 DCMi 31 56 71 + + − − − − HI-2 DCMi 39 31 61 + + − − − − KA-3 DCMi 69 36 60 + + − − − − PS-4 DCMi 60 34 76 + + − − − − BA-5 DCMi 67 43 59 + + − − − − DE-6 DCMi 31 52 57 + + − − − − CH-7 DCMi 62 51 73 + + − − − − GH-8 DCMi 45 34 62 + + − − − −   52.5 ± 17 (31–69) 42.0 ± 9.9 (31–56) 62.8 ± 7.8 (57–73)       RS-14 Cont 36 68 47 − − − − − − SM-15 Cont 46 61 49 − − − − − − KE-16 Cont 26 74 47 − − − − − − TU-17 Cont 36 64 50 − − − − − −   36.0 ± 8 (26–46) 66.8 ± 5.6 (61–74) 48.3 ± 1.2 (47–50)       EF LVEDD INFLAM PVB19 EV AdV HHV6 EBV High density microarray studies of human cardiac biopsies p p http://www.ncbi.nlm.nih.gov/projects/geo/ Quantitative real-time PCR analysis of human cardiac biopsies 6 2 Cardiovascular cell cultures Primary culture of neonatal rat cardiomyocytes (NRCMC) 7 3 8 2 6 Vascular endothelial cell line Quantitative real-time PCR analysis of activated cell cultures 2 2 2 Network analysis 1 http://www.ingenuity.com p Fig. 1 a c e nodes edges intensity of the node color red green various shapes Continuous edge lines broken edge lines .  b d f a c e red color green color brightness of the color  Statistical analysis t Δ Δ t p Results 1 1 http://www.ncbi.nlm.nih.gov/projects/geo/ q 1 1 2 2 2 q 2 p Table 2 http://www.ncbi.nlm.nih.gov/projects/geo/ 1 Network Symbol Regulation Factor q value Gene Name APN a Down 6.8 0.605 Adiponectin 14.4 CYR CXCL14 Down 5.9 1.943 Chemokine (C–X–C motif) ligand 14 4.4 AKT TDGF1 Down 4.7 0.605 Teratocarcinoma-derived growth factor 1 CYR PDGFA Down 3.6 0.371 Platelet-derived growth factor (PDGF)-α polypeptide APN SOS1 Down 3.1 0.371 Son of sevenless homolog 1 (Drosophila) CYR TMSB10 Down 2.6 0.371 Thymosin-β10 APN INSR Down 2.5 0.371 Insulin receptor CYR EGFR Down 2.5 2.226 Epidermal growth factor (EGF) receptor APN PIK3R1 Down 2.5 0.991 Phosphoinositide-3-kinase regulatory subunit 1 (p85α) CYR LAMA4 Down 2.4 0.371 Laminin α4 APN LMO4 Down 2.3 3.868 Lin-11, Isl-1, Mec-3 (LIM) domain only 4 CYR HSPG2 Down 2.1 2.226 Heparan sulfate proteoglycan 2  CYR SOX9 Down 2.1 0.371 Sex determining region Y (SRY)-box 9 APN LIFR Down 2.0 1.632 Leukemia inhibitory factor (LIF) receptor CYR TNXB Down 2.0 0.371 Tenascin XB AKT TGFBR3 Down 2.0 0.895 TGF-β receptor III (betaglycan) AKT EIF4EBP1 Down 2.0 2.345 Eukaryotic translation initiation factor 4E binding protein 1 CYR SLIT2 Down 2.0 1.667 Slit homolog 2 (Drosophila) CYR IGFBP5 Down 1.9 0.991 Insulin-like growth factor binding protein 5 CYR a Up 3.6 1.943 Cysteine-rich, angiogenic inducer, 61 3.3 CYR THBS1 Up 3.4 3.868 Thrombospondin 1 APN STAT1 Up 3.0 1.222 Signal transducer and activator of transcription 1 AKT ANKRD1 Up 3.0 2.226 Ankyrin repeat domain 1 (cardiac muscle) CYR ITGB1 Up 2.5 1.994 Integrin β1 = β-subunit of fibronectin receptor (CD29) AKT BDNF Up 2.4 3.641 Brain-derived neurotrophic factor AKT MATR3 Up 2.4 0.895 Matrin 3 APN JAK2 Up 2.3 3.469 Janus kinase 2 APN SLC16A1 Up 2.3 1.943 Solute carrier family 16 member 1 APN HBEFG Up 2.2 3.179 Heparin-binding EGF-like growth factor CYR CD47 Up 2.1 4.108 Integrin-associated signal transducer CYR FGF2 Up 2.1 2.868 Fibroblast growth factor (basic) APN SORT1 Up 2.1 1.632 Sortilin APN EPHA4 Up 2.1 2.345 EPH receptor A4 AKT STX16 Up 2.1 2.226 Syntaxin 16 CYR NES Up 2.0 2.487 Nestin CYR PDGFC Up 2.0 3.469 Platelet derived growth factor C CYR PTK2 Up 2.0 1.571 Protein tyrosine kinase 2 APN PTPN11 Up 2.0 1.632 Protein tyrosine phosphatase non-receptor type 11  AKT GOSR2 Up 2.0 1.667 Golgi SNAP receptor complex member 2 APN a Up 1.9 2.345 Nuclear factor of activated T cells 4 CYR BIRC4 Up 1.9 1.943 Baculoviral IAP repeat-containing 4 CYR HSXIAPA1 Up 1.9 2.487 XIAP associated factor-1 AKT PPP2R1B Up 1.9 3.641 Protein phosphatase 2 regulatory subunit A β APN SMARCA2 Up 1.9 2.226 SWI/SNF related matrix associated regulator of chromatin  AKT MID1 Up 1.9 3.175 Midline 1 AKT PARVA Up 1.8 2.621 Parvin-α APN LPL Up 1.8 2.487 Lipoprotein lipase CYR LAMA2 Up 1.8 1.994 Laminin-α2 AKT GSK3B Up 1.8 0.991 Glycogen synthase kinase 3β AKT PPP2R2A Up 1.8 1.222 Protein phosphatase 2 regulatory subunit B α APN SYNCRIP Up 1.8 1.994 Synaptotagmin binding RNA interacting protein AKT PPP2R2A Up 1.8 1.222 Protein phosphatase 2 regulatory subunit B α AKT UPF3A Up 1.8 3.173 UPF3 regulator of nonsense transcripts A  APN ADIPOR1 Up 1.7 2.868 Adiponectin receptor 1 CYR TFPI Up 1.7 3.868 Tissue factor pathway inhibitor APN SNX1 Up 1.7 4.362 Sorting nexin 1 APN SNX2 Up 1.7 4.467 Sorting nexin 2 APN RBBP4 Up 1.7 2.345 Retinoblastoma binding protein 4 AKT FBXO32 Up 1.7 2.487 F-box protein 32 AKT VPS33A Up 1.7 2.226 Vacuolar protein sorting 33A APN a Up 1.6 5.091 Nuclear factor of activated T cells 1 AKT a Up 1.6 4.108 Nuclear factor of activated T cells 3 APN JAK1 Up 1.6 1.994 Janus kinase 1 APN SP3 Up 1.6 2.226 Sp3 transcription factor AKT FRAP1 Up 1.6 4.362 FK506 binding protein 12 AKT STX6 Up 1.6 1.994 Syntaxin 6 CYR PRELP Up 1.6 4.757 Proline arginine-rich end leucine-rich repeat protein APN RALB Up 1.6 3.173 v-ral simian leukemia viral oncogene homolog B APN FGF13 Up 1.6 4.757 Fibroblast growth factor 13 APN TGFBR1 Up 1.6 4.108 Transforming growth factor-β receptor I AKT FTS Up 1.6 3.469 Fused toes homolog AKT AKT1 Up 1.5 4.757 v-akt AKT PPP2CA Up 1.5 4.362 Protein phosphatase 2 catalytic subunit α Affymetrix italics Affymetrix 2 a 8 q 1 1 1 1 9 10 2 2 q 2 Fig. 2 a b 3 a asterisks in shaded bars 14 Error bars b Error bars a  q 1 11 q 1 13 14 15 2 2 16 2 Discussion Identification of DCM subtypes 1 2 5 17 first second third Cardiac expression profile of DCMi 5 18 27 2 5 2+ 28 29 30 31 32 32 33 34 6 1 35 v 3 v 5 36 M 2 37 38 13 39 irreversible 39 33 42 knockout 40 41 40 41 40 41 9 10 2 54 55 10 43 44 14 15 45 46 47 48 49 50 51 52 53 54 55 Working model of local cardiac inflammation control 3 local local knockout 40 41 1 auto paracrine knockout systemic hormone-like 41 10 12 10 2 33 12 56 11 local Fig. 3 38 39 local knockout 38 39 systemic 10 right side of figure 8 left side center 2 left side right side 10 54 9 local right side left side  Limitations and perspective of the study 57 58 59 Conclusions 5 8 Electronic Supplementary Material Below is the link to the electronic supplementary material.
 Fig. S1 The disease phenotyping of the DCMi patient group (Table 1 and Patients and methods) that were investigated by genomewide Affymetrix microarray expression profiling included (in addition to clinical and molecular virological characterization) an immunohistochemical characterization of cardiac immune cell infiltration and vascular endothelial activation. The immunohistochemical studies were done on EMBs obtained by the same standard procedure as those used for the Affymetrix microarray expression profiling and for the TaqMan quantitative RT-PCRs (264.6 KB) (226.1 KB) (159.6 KB) Fig. S2 2 2 http://www.ncbi.nlm.nih.gov/projects/geo/ Sharp sign p p q q Table S1 2 1 Patients and methods http://www.ncbi.nlm.nih.gov/ projects/geo/