KEGG   PATHWAY: lav05414
Entry
lav05414                    Pathway                                
Name
Dilated cardiomyopathy - Loxodonta africana (African savanna elephant)
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
lav05414  Dilated cardiomyopathy
lav05414

Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100674420  ITGA1; integrin alpha-1 [KO:K06480]
100674705  ITGA2; integrin alpha-2 [KO:K06481]
100654429  ITGA2B; LOW QUALITY PROTEIN: integrin alpha-IIb [KO:K06476]
100671578  ITGA3; LOW QUALITY PROTEIN: integrin alpha-3 [KO:K06482]
100674409  ITGA4; integrin alpha-4 [KO:K06483]
100676951  ITGA5; integrin alpha-5 [KO:K06484]
100661035  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100665471  ITGA7; LOW QUALITY PROTEIN: integrin alpha-7 [KO:K06583]
100674808  ITGA8; integrin alpha-8 [KO:K06584]
100660884  ITGA9; LOW QUALITY PROTEIN: integrin alpha-9 [KO:K06585]
100667832  ITGA10; LOW QUALITY PROTEIN: integrin alpha-10 [KO:K06586]
100670461  ITGA11; integrin alpha-11 isoform X1 [KO:K06587]
100671252  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
100664978  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100660405  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
100671877  ITGB4; LOW QUALITY PROTEIN: integrin beta-4 [KO:K06525]
100676335  ITGB5; integrin beta-5 [KO:K06588]
100664907  ITGB6; integrin beta-6 isoform X1 [KO:K06589]
100661118  ITGB7; integrin beta-7 isoform X1 [KO:K06590]
100661984  ITGB8; integrin beta-8 isoform X1 [KO:K06591]
100667559  SSPN; sarcospan [KO:K22194]
100669677  SGCA; LOW QUALITY PROTEIN: alpha-sarcoglycan [KO:K12565]
100669307  SGCB; beta-sarcoglycan [KO:K12566]
100673202  SGCG; gamma-sarcoglycan isoform X1 [KO:K12564]
100654942  SGCD; delta-sarcoglycan [KO:K12563]
100668334  SGCE; epsilon-sarcoglycan [KO:K27061]
100672627  SGCZ; zeta-sarcoglycan isoform X1 [KO:K27062]
100672596  LAMA1; laminin subunit alpha-1 [KO:K05637]
100677404  LAMA2; laminin subunit alpha-2 [KO:K05637]
100675937  DAG1; dystroglycan [KO:K06265]
100663316  CAV3; LOW QUALITY PROTEIN: caveolin-3 [KO:K12959]
100673992  NOS1; nitric oxide synthase, brain isoform X2 [KO:K13240] [EC:1.14.13.39]
100663894  SNTA1; alpha-1-syntrophin [KO:K24063]
100667141  SNTB2; beta-2-syntrophin [KO:K24064]
100655910  SNTB1; beta-1-syntrophin [KO:K24064]
100672123  DTNA; dystrobrevin alpha isoform X6 [KO:K26998]
100659222  DES; desmin isoform X2 [KO:K07610]
100670743  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100654618  ACTB; actin, cytoplasmic 1 [KO:K05692]
104845494  LOW QUALITY PROTEIN: titin [KO:K12567] [EC:2.7.11.1]
100670991  TNNT2; troponin T, cardiac muscle [KO:K12045]
100660968  TNNC1; troponin C, slow skeletal and cardiac muscles isoform X1 [KO:K05865]
100658146  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
100666675  TPM1; tropomyosin alpha-1 chain isoform X5 [KO:K10373]
100653632  TPM2; tropomyosin beta chain isoform X3 [KO:K10374]
100674827  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
100671189  TPM4; tropomyosin alpha-4 chain [KO:K10375]
100665230  MYBPC3; myosin-binding protein C, cardiac-type [KO:K12568]
100656664  LOW QUALITY PROTEIN: myosin-binding protein C, fast-type [KO:K12568]
100656780  MYL3; myosin light chain 3 [KO:K12749]
100670087  myosin-6 isoform X1 [KO:K17751]
100670377  LOW QUALITY PROTEIN: myosin-7 [KO:K17751]
100667734  EMD; emerin [KO:K12569]
100662965  LMNA; lamin [KO:K12641]
104847364  uncharacterized protein LOC104847364 [KO:K06856]
100654973  ADRB1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141]
100655206  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
100669226  neuroendocrine secretory protein 55-like [KO:K04632]
100671072  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100673570  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100674724  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100675525  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
100670244  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100653532  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100653771  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100661616  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100663448  ADCY9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100656966  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100674245  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100659992  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100674649  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100673089  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
104846285  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
100673091  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
100653996  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X4 [KO:K04864]
100656938  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
100676022  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
100667110  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
100659138  CACNA2D3; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
100663604  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
100666105  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
100672366  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
100664775  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
100665821  CACNG5; voltage-dependent calcium channel gamma-5 subunit isoform X2 [KO:K04870]
111749631  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
100672020  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
100660460  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
100676989  ryanodine receptor 2 [KO:K04962]
100676453  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X2 [KO:K05853] [EC:7.2.2.10]
100671775  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X6 [KO:K05853] [EC:7.2.2.10]
100670753  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
100665933  PLN; cardiac phospholamban [KO:K05852]
100666349  SLC8A3; sodium/calcium exchanger 3 [KO:K05849]
100658790  SLC8A1; sodium/calcium exchanger 1 isoform X2 [KO:K05849]
100661888  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
100664710  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
100667634  TGFB1; transforming growth factor beta-1 [KO:K13375]
100656534  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
100653832  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
100677125  TNF; tumor necrosis factor isoform X2 [KO:K03156]
100670141  AGT; LOW QUALITY PROTEIN: 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
lav04260  Cardiac muscle contraction
lav04350  TGF-beta signaling pathway
lav04512  ECM-receptor interaction
lav04614  Renin-angiotensin system
lav05416  Viral myocarditis
KO pathway
ko05414   
LinkDB

DBGET integrated database retrieval system