KEGG   PATHWAY: umr05414
Entry
umr05414                    Pathway                                
Name
Dilated cardiomyopathy - Ursus maritimus (polar bear)
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
umr05414  Dilated cardiomyopathy
umr05414

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103664837  ITGA1; integrin alpha-1 isoform X1 [KO:K06480]
103664633  ITGA2; integrin alpha-2 [KO:K06481]
103665592  ITGA2B; integrin alpha-IIb [KO:K06476]
103660962  ITGA3; LOW QUALITY PROTEIN: integrin alpha-3 [KO:K06482]
103659636  ITGA4; integrin alpha-4 [KO:K06483]
103675680  ITGA5; integrin alpha-5 isoform X1 [KO:K06484]
103659892  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
103656923  ITGA7; integrin alpha-7 isoform X1 [KO:K06583]
103664242  ITGA8; integrin alpha-8 isoform X1 [KO:K06584]
103680775  ITGA9; integrin alpha-9 isoform X1 [KO:K06585]
103678405  ITGA10; integrin alpha-10 isoform X1 [KO:K06586]
103679149  ITGA11; integrin alpha-11 [KO:K06587]
103659655  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
103656511  ITGB1; integrin beta-1 [KO:K05719]
103665892  ITGB3; integrin beta-3 [KO:K06493]
103665746  ITGB4; integrin beta-4 [KO:K06525]
103678821  ITGB5; integrin beta-5 isoform X1 [KO:K06588]
103659497  ITGB6; integrin beta-6 isoform X1 [KO:K06589]
103675667  ITGB7; integrin beta-7 isoform X1 [KO:K06590]
103658858  ITGB8; integrin beta-8 [KO:K06591]
103665251  SSPN; sarcospan isoform X2 [KO:K22194]
103660442  SGCA; alpha-sarcoglycan [KO:K12565]
103672725  SGCB; beta-sarcoglycan [KO:K12566]
103664295  SGCG; gamma-sarcoglycan isoform X1 [KO:K12564]
103664549  SGCD; delta-sarcoglycan isoform X1 [KO:K12563]
103658739  SGCE; epsilon-sarcoglycan isoform X1 [KO:K27061]
103681331  SGCZ; zeta-sarcoglycan isoform X1 [KO:K27062]
103664656  LAMA1; laminin subunit alpha-1 [KO:K05637]
103663512  LAMA2; laminin subunit alpha-2 [KO:K05637]
103674820  DAG1; dystroglycan [KO:K06265]
103669585  CAV3; caveolin-3 [KO:K12959]
103661304  NOS1; nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
103674457  SNTA1; alpha-1-syntrophin isoform X1 [KO:K24063]
103673712  SNTB2; beta-2-syntrophin [KO:K24064]
103661667  SNTB1; beta-1-syntrophin [KO:K24064]
103663390  DTNA; dystrobrevin alpha [KO:K26998]
103668295  DMD; dystrophin isoform X1 [KO:K10366]
103662877  DES; desmin [KO:K07610]
103665813  ACTG1; actin, cytoplasmic 2 [KO:K05692]
103670086  ACTB; actin, cytoplasmic 1 [KO:K05692]
103659915  TTN; titin isoform X1 [KO:K12567] [EC:2.7.11.1]
103657704  TNNT2; troponin T, cardiac muscle isoform X3 [KO:K12045]
103675069  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
103679895  ACTC1; LOW QUALITY PROTEIN: actin, alpha cardiac muscle 1 [KO:K12314]
103676863  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
103667083  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
103668407  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
103668718  tropomyosin alpha-3 chain-like [KO:K09290]
103677161  TPM4; tropomyosin alpha-4 chain [KO:K10375]
103672388  MYBPC3; LOW QUALITY PROTEIN: myosin-binding protein C, cardiac-type [KO:K12568]
103675121  MYL3; myosin light chain 3 [KO:K12749]
103661279  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
103681067  MYH6; myosin-6 [KO:K17751]
103681068  myosin-7 [KO:K17751]
103679687  EMD; emerin isoform X1 [KO:K12569]
103668357  LMNA; lamin isoform X1 [KO:K12641]
121101313  ADRB1; beta-1 adrenergic receptor [KO:K04141]
103670935  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
103670936  neuroendocrine secretory protein 55 [KO:K04632]
103674675  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103679250  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103671685  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103679331  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
103678826  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103675618  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103673916  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
103661704  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103668547  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103662972  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103682183  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103675706  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
103674739  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
103667625  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
103657769  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
103661404  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
103664216  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
103675445  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
103659848  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
103658778  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
103675085  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
103674731  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
103675758  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
103665904  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
103676550  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
103668851  CACNG3; voltage-dependent calcium channel gamma-3 subunit isoform X1 [KO:K04868]
103665906  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
103665664  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
103672913  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
103672888  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
121103371  CACNG8; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
103662005  RYR2; ryanodine receptor 2 [KO:K04962]
103657815  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X3 [KO:K05853] [EC:7.2.2.10]
103667123  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
103661275  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
103663457  PLN; cardiac phospholamban [KO:K05852]
103674250  SLC8A3; LOW QUALITY PROTEIN: sodium/calcium exchanger 3 [KO:K05849]
103657216  SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849]
103671551  SLC8A1; sodium/calcium exchanger 1 [KO:K05849]
103676495  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
103677394  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
103658194  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
103670922  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
103682322  TNF; tumor necrosis factor [KO:K03156]
103661870  AGT; 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
umr04260  Cardiac muscle contraction
umr04350  TGF-beta signaling pathway
umr04512  ECM-receptor interaction
umr04614  Renin-angiotensin system
umr05416  Viral myocarditis
KO pathway
ko05414   
LinkDB

DBGET integrated database retrieval system