KEGG   PATHWAY: dle05414
Entry
dle05414                    Pathway                                
Name
Dilated cardiomyopathy - Delphinapterus leucas (beluga whale)
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
dle05414  Dilated cardiomyopathy
dle05414

Disease
H00294  Dilated cardiomyopathy
Organism
Delphinapterus leucas (beluga whale) [GN:dle]
Gene
111163079  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
111163908  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
111163985  AGT; angiotensinogen [KO:K09821]
111164225  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111164302  ITGA9; integrin alpha-9 [KO:K06585]
111164400  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
111164625  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
111164991  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111165040  PLN; cardiac phospholamban [KO:K05852]
111165200  SNTB1; beta-1-syntrophin isoform X1 [KO:K24064]
111166290  SGCA; alpha-sarcoglycan [KO:K12565]
111166330  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
111166388  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
111166617  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
111166674  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
111167038  LMNA; lamin isoform X1 [KO:K12641]
111167157  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
111168261  LAMA2; laminin subunit alpha-2 [KO:K05637]
111168318  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
111168340  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
111168402  DMD; dystrophin isoform X1 [KO:K10366]
111169490  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
111169866  SGCB; beta-sarcoglycan [KO:K12566]
111169961  CAV3; caveolin-3 [KO:K12959]
111170236  ITGA2B; integrin alpha-IIb [KO:K06476]
111170344  ACTB; actin, cytoplasmic 1 [KO:K05692]
111170610  EMD; emerin isoform X1 [KO:K12569]
111170657  TNF; tumor necrosis factor [KO:K03156]
111171621  ITGA4; integrin alpha-4 isoform X1 [KO:K06483]
111171639  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
111171650  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111171786  ITGB5; integrin beta-5 [KO:K06588]
111171858  DES; desmin [KO:K07610]
111172295  ADRB1; beta-1 adrenergic receptor [KO:K04141]
111172760  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
111172869  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
111172919  TTN; titin [KO:K12567] [EC:2.7.11.1]
111172949  ITGB6; integrin beta-6 isoform X1 [KO:K06589]
111173015  SLC8A3; sodium/calcium exchanger 3 [KO:K05849]
111173575  SGCZ; zeta-sarcoglycan [KO:K27062]
111173908  ITGA7; integrin alpha-7 isoform X1 [KO:K06583]
111173917  ITGA5; integrin alpha-5 [KO:K06484]
111173950  ITGB7; integrin beta-7 isoform X1 [KO:K06590]
111174035  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
111174049  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
111174141  TNNC1; troponin C, slow skeletal and cardiac muscles isoform X1 [KO:K05865]
111174274  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X2 [KO:K04860]
111174277  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
111174353  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
111174393  DAG1; dystroglycan [KO:K06265]
111174466  MYL3; myosin light chain 3 [KO:K12749]
111174776  [KO:K09290]
111174840  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
111175000  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111175161  SGCG; gamma-sarcoglycan [KO:K12564]
111176232  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
111176547  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
111176594  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
111176859  SSPN; sarcospan isoform X1 [KO:K22194]
111177477  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
111177687  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
111177762  ITGA11; integrin alpha-11 [KO:K06587]
111178037  ITGB1; integrin beta-1 [KO:K05719]
111178094  ITGA8; integrin alpha-8 isoform X1 [KO:K06584]
111178115  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
111178380  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111178556  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
111179587  SNTB2; beta-2-syntrophin [KO:K24064]
111179935  ITGA10; integrin alpha-10 [KO:K06586]
111180685  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
111180824  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
111180996  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
111181016  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
111181019  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
111181027  TNNI3; troponin I, cardiac muscle isoform X1 [KO:K12044]
111181122  SGCE; epsilon-sarcoglycan isoform X1 [KO:K27061]
111181513  DTNA; dystrobrevin alpha isoform X1 [KO:K26998]
111181781  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
111181944  ITGB8; integrin beta-8 [KO:K06591]
111182199  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
111182231  CACNG3; voltage-dependent calcium channel gamma-3 subunit isoform X1 [KO:K04868]
111182589  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
111182710  ACTG1; actin, cytoplasmic 2 [KO:K05692]
111182817  ITGB4; integrin beta-4 isoform X1 [KO:K06525]
111182918  CACNG5; voltage-dependent calcium channel gamma-5 subunit isoform X1 [KO:K04870]
111182919  CACNG4; voltage-dependent calcium channel gamma-4 subunit isoform X1 [KO:K04869]
111182970  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
111183148  SGCD; delta-sarcoglycan isoform X1 [KO:K12563]
111184070  MYBPC3; myosin-binding protein C, cardiac-type [KO:K12568]
111184279  SNTA1; alpha-1-syntrophin [KO:K24063]
111184534  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111185250  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111185895  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
111186741  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
111186746  [KO:K04632]
111186789  ITGA2; integrin alpha-2 [KO:K06481]
111186810  ITGA1; integrin alpha-1 [KO:K06480]
111186914  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
111186931  NOS1; nitric oxide synthase, brain isoform X1 [KO:K13240] [EC:1.14.13.39]
111187002  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
111187803  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
111187819  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
111188045  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
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
dle04260  Cardiac muscle contraction
dle04350  TGF-beta signaling pathway
dle04512  ECM-receptor interaction
dle04614  Renin-angiotensin system
dle05416  Viral myocarditis
KO pathway
ko05414   

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