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Entry
ko05414                     Pathway                                

Name
Dilated cardiomyopathy (DCM)
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 diseases
BRITE hierarchy
Pathway map
ko05414  Dilated cardiomyopathy (DCM)
ko05414

Ortholog table
Disease
H00294  Dilated cardiomyopathy
H00728  Brugada syndrome
Orthology
K06480  integrin alpha 1
K06481  integrin alpha 2
K06476  integrin alpha 2B
K06482  integrin alpha 3
K06483  integrin alpha 4
K06484  integrin alpha 5
K06485  integrin alpha 6
K06583  integrin alpha 7
K06584  integrin alpha 8
K06585  integrin alpha 9
K06586  integrin alpha 10
K06587  integrin alpha 11
K06487  integrin alpha V
K05719  integrin beta 1
K06493  integrin beta 3
K06525  integrin beta 4
K06588  integrin beta 5
K06589  integrin beta 6
K06590  integrin beta 7
K06591  integrin beta 8
K12563  delta-sarcoglycan
K12564  gamma-sarcoglycan
K12565  alpha-sarcoglycan
K12566  beta-sarcoglycan
K06265  dystroglycan 1
K07610  desmin
K10366  dystrophin
K05692  actin beta/gamma 1
K12567  titin [EC:2.7.11.1]
K12045  troponin T, cardiac muscle
K05865  troponin C, slow skeletal and cardiac muscles
K12044  troponin I, cardiac muscle
K12314  actin, alpha cardiac muscle
K10373  tropomyosin 1
K10374  tropomyosin 2
K09290  tropomyosin 3
K10375  tropomyosin 4
K12568  myosin-binding protein C, cardiac-type
K12749  myosin light chain 3
K10351  myosin regulatory light chain 2
K12569  emerin
K12641  lamin A/C
K06856  immunoglobulin heavy chain
K04141  adrenergic receptor beta-1
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08042  adenylate cyclase 2 [EC:4.6.1.1]
K08043  adenylate cyclase 3 [EC:4.6.1.1]
K08044  adenylate cyclase 4 [EC:4.6.1.1]
K08045  adenylate cyclase 5 [EC:4.6.1.1]
K08046  adenylate cyclase 6 [EC:4.6.1.1]
K08047  adenylate cyclase 7 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K04345  protein kinase A [EC:2.7.11.11]
K04850  voltage-dependent calcium channel L type alpha-1C
K04851  voltage-dependent calcium channel L type alpha-1D
K04853  voltage-dependent calcium channel L type alpha-1F
K04857  voltage-dependent calcium channel L type alpha-1S
K04862  voltage-dependent calcium channel beta-1
K04863  voltage-dependent calcium channel beta-2
K04864  voltage-dependent calcium channel beta-3
K04865  voltage-dependent calcium channel beta-4
K04858  voltage-dependent calcium channel alpha-2/delta-1
K04859  voltage-dependent calcium channel alpha-2/delta-2
K04860  voltage-dependent calcium channel alpha-2/delta-3
K04861  voltage-dependent calcium channel alpha-2/delta-4
K04866  voltage-dependent calcium channel gamma-1
K04867  voltage-dependent calcium channel gamma-2
K04868  voltage-dependent calcium channel gamma-3
K04869  voltage-dependent calcium channel gamma-4
K04870  voltage-dependent calcium channel gamma-5
K04871  voltage-dependent calcium channel gamma-6
K04872  voltage-dependent calcium channel gamma-7
K04873  voltage-dependent calcium channel gamma-8
K04962  ryanodine receptor 2
K05852  phospholamban
K05459  insulin-like growth factor 1
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K03156  tumor necrosis factor superfamily, member 2
Compound
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
C01330  Sodium cation
C02135  Angiotensin II
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
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