KEGG   PATHWAY: epz05414
Entry
epz05414                    Pathway                                
Name
Dilated cardiomyopathy - Equus przewalskii (Przewalski's horse)
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
epz05414  Dilated cardiomyopathy
epz05414

Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103558069  ITGA1; integrin subunit alpha 1 [KO:K06480]
103558080  ITGA2; integrin subunit alpha 2 [KO:K06481]
103551206  ITGA2B; integrin subunit alpha 2b [KO:K06476]
103551055  ITGA3; integrin subunit alpha 3 [KO:K06482]
103540739  integrin alpha-4 [KO:K06483]
103563237  ITGA5; integrin subunit alpha 5 [KO:K06484]
103553123  ITGA6; integrin subunit alpha 6 [KO:K06485]
103560209  ITGA7; integrin subunit alpha 7 [KO:K06583]
103559616  integrin alpha-8 [KO:K06584]
103553903  ITGA9; integrin subunit alpha 9 [KO:K06585]
103556229  ITGA10; integrin subunit alpha 10 [KO:K06586]
103554819  ITGA11; integrin subunit alpha 11 [KO:K06587]
103557856  ITGAV; integrin subunit alpha V [KO:K06487]
103565316  ITGB1; integrin subunit beta 1 [KO:K05719]
103560746  ITGB3; integrin subunit beta 3 [KO:K06493]
103546589  ITGB4; integrin subunit beta 4 [KO:K06525]
103547475  ITGB5; integrin subunit beta 5 [KO:K06588]
103546835  ITGB6; integrin subunit beta 6 [KO:K06589]
103559421  ITGB7; integrin subunit beta 7 [KO:K06590]
103559760  ITGB8; integrin subunit beta 8 [KO:K06591]
103546620  SSPN; sarcospan [KO:K22194]
103549572  SGCA; sarcoglycan alpha [KO:K12565]
103548502  SGCB; sarcoglycan beta [KO:K12566]
103559651  SGCG; sarcoglycan gamma [KO:K12564]
103547577  SGCD; sarcoglycan delta [KO:K12563]
103553628  SGCE; sarcoglycan epsilon [KO:K27061]
103552993  LAMA2; laminin subunit alpha 2 [KO:K05637]
103564595  LAMA1; laminin subunit alpha 1 [KO:K05637]
103553414  DAG1; dystroglycan 1 [KO:K06265]
103559029  CAV3; caveolin 3 [KO:K12959]
103547950  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
103561309  SNTA1; syntrophin alpha 1 [KO:K24063]
103563760  SNTB2; syntrophin beta 2 [KO:K24064]
103557099  DTNA; dystrobrevin alpha [KO:K26998]
103557453  DES; desmin [KO:K07610]
103551082  ACTG1; actin gamma 1 [KO:K05692]
103547895  ACTB; actin beta [KO:K05692]
103547978  titin [KO:K12567] [EC:2.7.11.1]
103547965  titin-like [KO:K12567] [EC:2.7.11.1]
103540440  troponin T, cardiac muscle-like [KO:K12045]
103546497  TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
103562864  TNNI3; troponin I3, cardiac type [KO:K12044]
103549173  ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
103552579  TPM1; tropomyosin 1 (alpha) [KO:K10373]
103560300  TPM2; tropomyosin 2 (beta) [KO:K10374]
103555405  TPM3; tropomyosin 3 [KO:K09290]
103540448  TPM4; tropomyosin 4 [KO:K10375]
103561120  MYBPC3; myosin binding protein C, cardiac [KO:K12568]
103551037  MYL3; myosin light chain 3 [KO:K12749]
103544050  myosin regulatory light chain 2, ventricular/cardiac muscle isoform-like [KO:K10351]
103563014  myosin-7-like [KO:K17751]
103563015  myosin-6 [KO:K17751]
103548822  LMNA; lamin A/C [KO:K12641]
103562625  uncharacterized LOC103562625 [KO:K06856]
103562621  putative V-set and immunoglobulin domain-containing protein 7 [KO:K06856]
103565402  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103547036  neuroendocrine secretory protein 55 [KO:K04632]
103550430  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103562505  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
103547823  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103561050  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103563830  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103563634  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103556685  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103565019  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
103567623  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103553014  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103557289  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103565953  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103560754  voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
103543955  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
103565109  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
103552950  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
103558314  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
103552221  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
103558127  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
103560846  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
103559270  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
103565858  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
103560835  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
103563202  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
103559910  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
103541534  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
103563203  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
103563201  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
103556198  CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
103556197  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
103554178  RYR2; ryanodine receptor 2 [KO:K04962]
103558311  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
103562734  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
103541478  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
103559610  PLN; phospholamban [KO:K05852]
103552905  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
103562245  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
103549360  IGF1; insulin like growth factor 1 [KO:K05459]
103562543  TGFB1; transforming growth factor beta 1 [KO:K13375]
103543045  TGFB2; transforming growth factor beta 2 [KO:K13376]
103555506  TGFB3; transforming growth factor beta 3 [KO:K13377]
103562469  TNF; tumor necrosis factor [KO:K03156]
103561130  AGT; angiotensinogen [KO:K09821]
Compound
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
C01330  Sodium cation
Reference
  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
  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
  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
  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
  Authors
Towbin JA, Bowles NE
  Title
The failing heart.
  Journal
Nature 415:227-33 (2002)
DOI:10.1038/415227a
Reference
  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
  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
  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
  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
  Authors
Liu PP, Mason JW
  Title
Advances in the understanding of myocarditis.
  Journal
Circulation 104:1076-82 (2001)
DOI:10.1161/hc3401.095198
Reference
  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
epz04260  Cardiac muscle contraction
epz04350  TGF-beta signaling pathway
epz04512  ECM-receptor interaction
epz04614  Renin-angiotensin system
epz05416  Viral myocarditis
KO pathway
ko05414   
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