KEGG   PATHWAY: pvp05414
Entry
pvp05414                    Pathway                                
Name
Dilated cardiomyopathy - Pteropus vampyrus (large flying fox)
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
pvp05414  Dilated cardiomyopathy
pvp05414

Disease
H00294  Dilated cardiomyopathy
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288607  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
105288745  ITGA9; integrin alpha-9 [KO:K06585]
105288850  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105289209  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
105289221  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
105289401  NOS1; LOW QUALITY PROTEIN: nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
105289673  ITGAV; LOW QUALITY PROTEIN: integrin alpha-V [KO:K06487]
105289813  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105289920  SGCD; delta-sarcoglycan isoform X2 [KO:K12563]
105290034  MYBPC3; myosin-binding protein C, cardiac-type [KO:K12568]
105290414  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
105291105  DES; LOW QUALITY PROTEIN: desmin [KO:K07610]
105291118  ITGB6; integrin beta-6 isoform X4 [KO:K06589]
105291172  PLN; cardiac phospholamban [KO:K05852]
105291179  LAMA2; laminin subunit alpha-2 [KO:K05637]
105291472  ADRB1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141]
105291916  ITGA4; integrin alpha-4 [KO:K06483]
105291923  TTN; titin [KO:K12567] [EC:2.7.11.1]
105291989  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
105292087  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105292163  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
105292568  SNTB1; beta-1-syntrophin [KO:K24064]
105292942  SLC8A1; sodium/calcium exchanger 1 isoform X4 [KO:K05849]
105293216  DTNA; dystrobrevin alpha isoform X2 [KO:K26998]
105293285  SGCG; gamma-sarcoglycan [KO:K12564]
105293425  ITGB4; integrin beta-4 [KO:K06525]
105293783  SGCB; beta-sarcoglycan isoform X1 [KO:K12566]
105293829  ITGB8; integrin beta-8 isoform X1 [KO:K06591]
105294064  SSPN; sarcospan [KO:K22194]
105294261  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
105294327  SGCE; epsilon-sarcoglycan isoform X1 [KO:K27061]
105294565  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
105294917  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
105295184  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
105295407  SGCA; alpha-sarcoglycan isoform X1 [KO:K12565]
105295411  ITGA3; integrin alpha-3 isoform X2 [KO:K06482]
105295536  [KO:K04858]
105295568  SGCZ; zeta-sarcoglycan [KO:K27062]
105296083  [KO:K04632]
105296163  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105296207  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
105296349  LMNA; lamin isoform X1 [KO:K12641]
105296457  TPM3; tropomyosin alpha-3 chain [KO:K09290]
105296655  TPM4; tropomyosin alpha-4 chain [KO:K10375]
105296936  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
105296939  TNNT2; troponin T, cardiac muscle [KO:K12045]
105297298  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
105297299  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
105297518  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105297519  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
105297528  ITGB5; integrin beta-5 [KO:K06588]
105297752  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
105297753  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
105297754  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
105297781  ITGA10; integrin alpha-10 [KO:K06586]
105299067  CAV3; caveolin-3 [KO:K12959]
105299206  TGFB3; transforming growth factor beta-3 [KO:K13377]
105299581  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105300372  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
105300547  [KO:K17751]
105300548  [KO:K17751]
105301152  ACTG1; actin, cytoplasmic 2 [KO:K05692]
105301250  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105302340  MYL3; myosin light chain 3 [KO:K12749]
105302390  DAG1; dystroglycan [KO:K06265]
105302493  EMD; emerin [KO:K12569]
105302613  ITGA7; integrin alpha-7 isoform X1 [KO:K06583]
105302663  ITGB7; integrin beta-7 [KO:K06590]
105302702  ITGA5; integrin alpha-5 [KO:K06484]
105303008  ITGB1; integrin beta-1 [KO:K05719]
105303095  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105303446  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
105303529  ITGA2B; integrin alpha-IIb [KO:K06476]
105304212  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
105304275  SNTA1; alpha-1-syntrophin [KO:K24063]
105304362  [KO:K04860]
105304363  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
105304409  DMD; dystrophin isoform X1 [KO:K10366]
105304583  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
105304920  TNNI3; troponin I, cardiac muscle [KO:K12044]
105305015  ITGA8; integrin alpha-8 isoform X1 [KO:K06584]
105305325  TNF; tumor necrosis factor [KO:K03156]
105305779  [KO:K24064]
105306022  AGT; angiotensinogen [KO:K09821]
105306461  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
105307907  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
105307927  ITGA2; integrin alpha-2 isoform X1 [KO:K06481]
105307929  ITGA1; integrin alpha-1 [KO:K06480]
105307945  TGFB1; transforming growth factor beta-1 [KO:K13375]
105308299  [KO:K08041] [EC:4.6.1.1]
105308383  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105308817  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
105309056  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105309400  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105309463  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
105309464  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
105309480  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
105310162  [KO:K12045]
105310261  ITGA11; integrin alpha-11 [KO:K06587]
105310714  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
105311392  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
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
pvp04260  Cardiac muscle contraction
pvp04350  TGF-beta signaling pathway
pvp04512  ECM-receptor interaction
pvp04614  Renin-angiotensin system
pvp05416  Viral myocarditis
KO pathway
ko05414   

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