KEGG   PATHWAY: aml05414
Entry
aml05414                    Pathway                                
Name
Dilated cardiomyopathy - Ailuropoda melanoleuca (giant panda)
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
aml05414  Dilated cardiomyopathy
aml05414

Disease
H00294  Dilated cardiomyopathy
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100463584  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
100463812  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X5 [KO:K04858]
100464104  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X2 [KO:K04865]
100464234  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
100464670  ITGA4; integrin alpha-4 isoform X1 [KO:K06483]
100465047  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
100465284  CACNG7; voltage-dependent calcium channel gamma-7 subunit isoform X3 [KO:K04872]
100465655  PLN; cardiac phospholamban [KO:K05852]
100465699  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X6 [KO:K05853] [EC:7.2.2.10]
100465788  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
100465830  LAMA1; laminin subunit alpha-1 [KO:K05637]
100465955  TPM1; tropomyosin alpha-1 chain isoform X15 [KO:K10373]
100466054  MYL3; myosin light chain 3 [KO:K12749]
100466132  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100466169  SGCG; gamma-sarcoglycan isoform X1 [KO:K12564]
100466965  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100467299  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
100467396  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
100467566  DTNA; dystrobrevin alpha isoform X19 [KO:K26998]
100467700  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100468087  NOS1; nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
100468149  ITGB8; integrin beta-8 isoform X1 [KO:K06591]
100468252  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100468661  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
100469020  DES; desmin [KO:K07610]
100469231  [KO:K04632]
100469411  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
100469610  SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849]
100469628  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100469629  LMNA; lamin [KO:K12641]
100469928  ITGB4; integrin beta-4 isoform X1 [KO:K06525]
100469933  [KO:K17751]
100470137  AGT; angiotensinogen [KO:K09821]
100470185  MYH6; LOW QUALITY PROTEIN: myosin-6 [KO:K17751]
100470703  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
100470716  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
100470823  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
100471103  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
100471164  ADCY3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
100471252  ADRB1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141]
100471563  TNF; tumor necrosis factor [KO:K03156]
100471638  TNNI3; troponin I, cardiac muscle [KO:K12044]
100471721  ITGB6; integrin beta-6 isoform X3 [KO:K06589]
100471755  SLC8A3; sodium/calcium exchanger 3 isoform X2 [KO:K05849]
100471940  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100472010  SGCZ; zeta-sarcoglycan [KO:K27062]
100472670  SNTA1; alpha-1-syntrophin isoform X1 [KO:K24063]
100472777  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100472835  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
100473119  CAV3; caveolin-3 [KO:K12959]
100473195  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100473254  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
100473680  [KO:K04632]
100474079  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100474121  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100474212  ITGB7; integrin beta-7 [KO:K06590]
100474541  [KO:K05849]
100474561  SNTB2; beta-2-syntrophin [KO:K24064]
100474630  SGCE; epsilon-sarcoglycan isoform X3 [KO:K27061]
100475193  SGCD; delta-sarcoglycan isoform X1 [KO:K12563]
100475280  ITGA7; integrin alpha-7 isoform X1 [KO:K06583]
100475723  DAG1; dystroglycan [KO:K06265]
100475861  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
100476063  MYBPC3; myosin-binding protein C, cardiac-type [KO:K12568]
100476147  ITGA1; integrin alpha-1 isoform X2 [KO:K06480]
100476165  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
100476256  ITGB3; integrin beta-3 [KO:K06493]
100476315  CACNG5; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
100476382  ITGB5; integrin beta-5 isoform X1 [KO:K06588]
100476403  ITGA2; integrin alpha-2 [KO:K06481]
100476488  SGCA; alpha-sarcoglycan isoform X1 [KO:K12565]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100476576  RYR2; LOW QUALITY PROTEIN: ryanodine receptor 2 [KO:K04962]
100476638  TTN; LOW QUALITY PROTEIN: titin [KO:K12567] [EC:2.7.11.1]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100477000  CACNG3; voltage-dependent calcium channel gamma-3 subunit isoform X1 [KO:K04868]
100477567  SGCB; beta-sarcoglycan [KO:K12566]
100478512  ITGA8; integrin alpha-8 isoform X1 [KO:K06584]
100479237  ITGA11; integrin alpha-11 isoform X1 [KO:K06587]
100479433  ITGA5; integrin alpha-5 [KO:K06484]
100479654  SSPN; sarcospan isoform X1 [KO:K22194]
100479715  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X3 [KO:K04850]
100479748  ITGA3; integrin alpha-3 [KO:K06482]
100479948  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X2 [KO:K04864]
100480223  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
100480310  ITGA9; integrin alpha-9 [KO:K06585]
100480599  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
100480767  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
100481020  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
100482519  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100482697  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100482767  TPM3; tropomyosin alpha-3 chain isoform X7 [KO:K09290]
100483724  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
100483814  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
100483894  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
100483911  EMD; emerin isoform X2 [KO:K12569]
100483953  ITGA10; integrin alpha-10 isoform X1 [KO:K06586]
100484185  ITGA2B; integrin alpha-IIb [KO:K06476]
100484712  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
100484758  DMD; dystrophin isoform X11 [KO:K10366]
100484935  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
105240357  SNTB1; beta-1-syntrophin [KO:K24064]
117799519  [KO:K12749]
117799593  [KO:K10373]
117799607  [KO:K09290]
117800105  [KO:K10373]
117800125  [KO:K05692]
117800158  [KO:K05865]
117800181  [KO:K05692]
117800361  [KO:K05692]
117800408  [KO:K05692]
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
aml04260  Cardiac muscle contraction
aml04350  TGF-beta signaling pathway
aml04512  ECM-receptor interaction
aml04614  Renin-angiotensin system
aml05416  Viral myocarditis
KO pathway
ko05414   

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