KEGG   PATHWAY: pcw05414
Entry
pcw05414                    Pathway                                
Name
Dilated cardiomyopathy - Phascolarctos cinereus (koala)
Description
Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM ("familial" DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of "familial" DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an "idiopathic" DCM. Current hypotheses regarding causes of "idiopathic" DCM focus on myocarditis induced by enterovirus and subsequent autoimmune myocardium impairments. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with "idiopathic" DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure.
Class
Human Diseases; Cardiovascular disease
Pathway map
pcw05414  Dilated cardiomyopathy
pcw05414

Organism
Phascolarctos cinereus (koala) [GN:pcw]
Gene
110215414  ITGA1; integrin alpha-1 isoform X1 [KO:K06480]
110215432  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
110215866  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
110215841  ITGA3; integrin alpha-3 [KO:K06482]
110221680  ITGA4; integrin alpha-4 [KO:K06483]
110194038  ITGA5; integrin alpha-5 [KO:K06484]
110211575  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
110210894  ITGA7; LOW QUALITY PROTEIN: integrin alpha-7 [KO:K06583]
110209198  ITGA8; integrin alpha-8 isoform X1 [KO:K06584]
110203090  ITGA9; integrin alpha-9 [KO:K06585]
110219961  ITGA10; integrin alpha-10 isoform X1 [KO:K06586]
110205706  ITGA11; integrin alpha-11 isoform X1 [KO:K06587]
110201716  ITGAV; integrin alpha-V [KO:K06487]
110211245  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
110215904  ITGB3; integrin beta-3 [KO:K06493]
110219298  ITGB4; LOW QUALITY PROTEIN: integrin beta-4 [KO:K06525]
110208137  ITGB5; integrin beta-5 [KO:K06588]
110220737  ITGB6; integrin beta-6 [KO:K06589]
110194074  ITGB7; LOW QUALITY PROTEIN: integrin beta-7 [KO:K06590]
110213049  ITGB8; integrin beta-8 isoform X1 [KO:K06591]
110193374  SSPN; sarcospan [KO:K22194]
110215752  SGCA; alpha-sarcoglycan isoform X1 [KO:K12565]
110211038  SGCB; beta-sarcoglycan [KO:K12566]
110215625  SGCG; gamma-sarcoglycan isoform X1 [KO:K12564]
110199726  SGCD; delta-sarcoglycan [KO:K12563]
110217631  SGCE; epsilon-sarcoglycan isoform X1 [KO:K27061]
110203138  SGCZ; zeta-sarcoglycan isoform X1 [KO:K27062]
110208858  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
110199966  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
110216898  DAG1; dystroglycan isoform X1 [KO:K06265]
110199079  CAV3; caveolin-3 [KO:K12959]
110222812  NOS1; LOW QUALITY PROTEIN: nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
110216808  SNTA1; alpha-1-syntrophin isoform X1 [KO:K24063]
110210261  SNTB2; beta-2-syntrophin [KO:K24064]
110193274  SNTB1; beta-1-syntrophin [KO:K24064]
110212517  DTNA; dystrobrevin alpha isoform X1 [KO:K26998]
110198777  LOW QUALITY PROTEIN: dystrophin-like [KO:K10366]
110219459  DES; desmin [KO:K07610]
110218220  ACTG1; actin, cytoplasmic 2 [KO:K05692]
110205635  actin, cytoplasmic 1-like [KO:K05692]
110214034  LOW QUALITY PROTEIN: actin, cytoplasmic type 5-like [KO:K05692]
110223114  ACTB; actin, cytoplasmic 1 [KO:K05692]
110211623  TTN; LOW QUALITY PROTEIN: titin [KO:K12567] [EC:2.7.11.1]
110211624  LOW QUALITY PROTEIN: muscle M-line assembly protein unc-89-like [KO:K12567] [EC:2.7.11.1]
110219553  TNNT2; LOW QUALITY PROTEIN: troponin T, cardiac muscle [KO:K12045]
110197564  TNNC1; LOW QUALITY PROTEIN: troponin C, slow skeletal and cardiac muscles [KO:K05865]
110220013  TNNI3; troponin I, cardiac muscle [KO:K12044]
110214160  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
110195734  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
110201444  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
110211987  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
110196120  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
110223922  MYBPC3; myosin-binding protein C, cardiac-type isoform X1 [KO:K12568]
110217119  MYL3; myosin light chain 3 [KO:K12749]
110196868  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
110193568  MYH7; myosin-7 [KO:K17751]
110193748  MYH6; myosin-6 [KO:K17751]
110200366  EMD; emerin [KO:K12569]
110211929  LMNA; lamin [KO:K12641]
110214297  immunoglobulin alpha-2 heavy chain-like isoform X1 [KO:K06856]
110214304  Ig heavy chain Mem5-like [KO:K06856]
110209527  ADRB1; beta-1 adrenergic receptor isoform X1 [KO:K04141]
110205152  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
110197533  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110220436  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
110206523  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
110197384  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
110208122  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110201474  ADCY6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
110207473  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
110216073  ADCY8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
110214660  ADCY9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
110209926  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
110214178  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110199822  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
110218748  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
110197022  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
110201034  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
110219570  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
110215900  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
110194513  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
110201498  CACNB3; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864]
110196898  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
110206948  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
110217120  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
110197042  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
110218752  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
110218302  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
110205730  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
110214472  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
110218341  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
110219947  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
110220167  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
110219858  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
110217820  RYR2; LOW QUALITY PROTEIN: ryanodine receptor 2 [KO:K04962]
110196847  ATP2A2; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
110222056  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
110193109  ATP2A3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
110197571  PLN; cardiac phospholamban [KO:K05852]
110218488  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
110208379  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
110202404  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
110205653  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
110202366  TGFB1; transforming growth factor beta-1 [KO:K13375]
110205565  TGFB2; LOW QUALITY PROTEIN: transforming growth factor beta-2 [KO:K13376]
110208305  TGFB3; transforming growth factor beta-3 [KO:K13377]
110199397  TNF; tumor necrosis factor [KO:K03156]
110217880  AGT; angiotensinogen [KO:K09821]
Compound
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
C01330  Sodium cation
Reference
PMID:12270949
  Authors
Fatkin D, Graham RM
  Title
Molecular mechanisms of inherited cardiomyopathies.
  Journal
Physiol Rev 82:945-80 (2002)
DOI:10.1152/physrev.00012.2002
Reference
PMID:18672201
  Authors
Lappe JM, Pelfrey CM, Tang WH
  Title
Recent insights into the role of autoimmunity in idiopathic dilated cardiomyopathy.
  Journal
J Card Fail 14:521-30 (2008)
DOI:10.1016/j.cardfail.2008.02.016
Reference
PMID:19273156
  Authors
Zhao P, Sharma AC, Ren J
  Title
Pathogenesis and therapy of autoimmunity-induced dilated cardiomyopathy.
  Journal
Front Biosci 14:1708-15 (2009)
DOI:10.2741/3334
Reference
PMID:11716909
  Authors
Franz WM, Muller OJ, Katus HA
  Title
Cardiomyopathies: from genetics to the prospect of treatment.
  Journal
Lancet 358:1627-37 (2001)
DOI:10.1016/S0140-6736(01)06657-0
Reference
PMID:11805847
  Authors
Towbin JA, Bowles NE
  Title
The failing heart.
  Journal
Nature 415:227-33 (2002)
DOI:10.1038/415227a
Reference
PMID:19017683
  Authors
Luk A, Ahn E, Soor GS, Butany J
  Title
Dilated cardiomyopathy: a review.
  Journal
J Clin Pathol 62:219-25 (2009)
DOI:10.1136/jcp.2008.060731
Reference
PMID:19246813
  Authors
Yoshikawa T, Baba A, Nagatomo Y
  Title
Autoimmune mechanisms underlying dilated cardiomyopathy.
  Journal
Circ J 73:602-7 (2009)
DOI:10.1253/circj.CJ-08-1151
Reference
PMID:14522402
  Authors
Mason JW
  Title
Myocarditis and dilated cardiomyopathy: an inflammatory link.
  Journal
Cardiovasc Res 60:5-10 (2003)
DOI:10.1016/S0008-6363(03)00437-1
Reference
PMID:15146239
  Authors
Jahns R, Boivin V, Hein L, Triebel S, Angermann CE, Ertl G, Lohse MJ
  Title
Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy.
  Journal
J Clin Invest 113:1419-29 (2004)
DOI:10.1172/JCI20149
Reference
PMID:11524405
  Authors
Liu PP, Mason JW
  Title
Advances in the understanding of myocarditis.
  Journal
Circulation 104:1076-82 (2001)
DOI:10.1161/hc3401.095198
Reference
PMID:16817756
  Authors
Tam PE
  Title
Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.
  Journal
Viral Immunol 19:133-46 (2006)
DOI:10.1089/vim.2006.19.133
Related
pathway
pcw04260  Cardiac muscle contraction
pcw04350  TGF-beta signaling pathway
pcw04512  ECM-receptor interaction
pcw04614  Renin-angiotensin system
pcw05416  Viral myocarditis
KO pathway
ko05414   
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