KEGG   PATHWAY: ngi05414
Entry
ngi05414                    Pathway                                
Name
Dilated cardiomyopathy - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi05414  Dilated cardiomyopathy
ngi05414

Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103734043  Itga1; integrin subunit alpha 1 [KO:K06480]
103734059  Itga2; integrin subunit alpha 2 [KO:K06481]
103738294  Itga2b; integrin subunit alpha 2b [KO:K06476]
103738376  Itga3; integrin subunit alpha 3 [KO:K06482]
103729874  Itga4; integrin subunit alpha 4 [KO:K06483]
103738966  Itga5; integrin subunit alpha 5 [KO:K06484]
103751741  Itga6; integrin subunit alpha 6 [KO:K06485]
103738830  Itga7; integrin subunit alpha 7 [KO:K06583]
103734817  Itga8; integrin subunit alpha 8 [KO:K06584]
103752249  Itga9; integrin subunit alpha 9 [KO:K06585]
103729511  Itga10; integrin subunit alpha 10 [KO:K06586]
103736909  Itga11; integrin subunit alpha 11 [KO:K06587]
103728788  Itgav; integrin subunit alpha V [KO:K06487]
103745645  Itgb1; integrin subunit beta 1 [KO:K05719]
103724762  Itgb3; integrin subunit beta 3 [KO:K06493]
103732717  Itgb4; integrin subunit beta 4 [KO:K06525]
103741999  Itgb5; integrin subunit beta 5 [KO:K06588]
103744081  Itgb6; integrin subunit beta 6 [KO:K06589]
103738472  Itgb7; integrin subunit beta 7 [KO:K06590]
103733702  Itgb8; integrin subunit beta 8 [KO:K06591]
103746717  Sspn; sarcospan [KO:K22194]
103738381  Sgca; sarcoglycan alpha [KO:K12565]
103732281  Sgcb; sarcoglycan beta [KO:K12566]
103727186  Sgcg; sarcoglycan gamma [KO:K12564]
103744221  Sgcd; sarcoglycan delta [KO:K12563]
103725224  Sgce; sarcoglycan epsilon [KO:K27061]
103744327  Sgcz; sarcoglycan zeta [KO:K27062]
103735414  Lama1; laminin subunit alpha 1 [KO:K05637]
103740954  laminin subunit alpha-1-like [KO:K05637]
103729744  Lama2; laminin subunit alpha 2 [KO:K05637]
103750183  Dag1; dystroglycan 1 [KO:K06265]
103751406  Cav3; caveolin 3 [KO:K12959]
103745523  Nos1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
103743783  Snta1; syntrophin alpha 1 [KO:K24063]
103734780  Sntb2; syntrophin beta 2 [KO:K24064]
103738151  Sntb1; syntrophin beta 1 [KO:K24064]
103750594  Dtna; dystrobrevin alpha [KO:K26998]
103727757  Des; desmin [KO:K07610]
103730387  Actg1; actin gamma 1 [KO:K05692]
103748659  Actb; actin beta [KO:K05692]
103751793  Ttn; titin [KO:K12567] [EC:2.7.11.1]
103731818  Tnnt2; troponin T2, cardiac type [KO:K12045]
103749000  Tnnc1; troponin C1, slow skeletal and cardiac type [KO:K05865]
103744862  Tnni3; troponin I3, cardiac type [KO:K12044]
103740516  Actc1; actin, alpha, cardiac muscle 1 [KO:K12314]
103750083  Tpm1; tropomyosin 1 (alpha) [KO:K10373]
103741541  Tpm2; tropomyosin 2 (beta) [KO:K10374]
103751563  Tpm3; tropomyosin 3 [KO:K09290]
103726930  Tpm4; tropomyosin 4 [KO:K10375]
103742511  Mybpc3; myosin binding protein C, cardiac [KO:K12568]
103732019  Myl3; myosin light chain 3 [KO:K12749]
103745580  Myl2; myosin light chain 2 [KO:K10351]
103739454  Myh7; myosin-7 [KO:K17751]
103739453  Myh6; myosin-6 [KO:K17751]
103731217  Emd; emerin [KO:K12569]
103750617  Lmna; lamin A/C [KO:K12641]
103751925  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
103726091  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
103731758  Adrb1; adrenoceptor beta 1 [KO:K04141]
103741475  Gnas; GNAS complex locus [KO:K04632]
103741466  neuroendocrine secretory protein 55 [KO:K04632]
103741433  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103735350  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
103746460  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103739411  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103741989  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103750558  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103730120  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103743923  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103744458  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103751850  Prkaca; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103728095  Prkacb; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103739378  Cacna1c; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
103749025  Cacna1d; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
103741673  Cacna1f; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
103731814  Cacna1s; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
103743810  Cacnb1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
103726514  Cacnb2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
103750559  Cacnb3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
103738122  Cacnb4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
103730725  Cacna2d1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
103750148  Cacna2d2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
103749031  Cacna2d3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
103739384  Cacna2d4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
103742198  Cacng1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
103748628  Cacng2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
103746927  Cacng3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
103742200  Cacng4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
103742201  Cacng5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
103729669  Cacng6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
103729667  Cacng7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
103729702  Cacng8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873]
103743548  ryanodine receptor 2-like [KO:K04962]
103726408  Atp2a1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
103751990  Atp2a3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
103739078  Atp2a2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
103736294  Pln; phospholamban [KO:K05852]
103736381  Slc8a1; solute carrier family 8 member A1 [KO:K05849]
103744201  Slc8a3; solute carrier family 8 member A3 [KO:K05849]
103724972  Slc8a2; solute carrier family 8 member A2 [KO:K05849]
103733723  Igf1; insulin like growth factor 1 [KO:K05459]
103751514  Tgfb1; transforming growth factor beta 1 [KO:K13375]
103728817  Tgfb2; transforming growth factor beta 2 [KO:K13376]
103739777  Tgfb3; transforming growth factor beta 3 [KO:K13377]
103724452  Tnf; tumor necrosis factor [KO:K03156]
103744123  Agt; angiotensinogen [KO:K09821]
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
ngi04260  Cardiac muscle contraction
ngi04350  TGF-beta signaling pathway
ngi04512  ECM-receptor interaction
ngi04614  Renin-angiotensin system
ngi05416  Viral myocarditis
KO pathway
ko05414   
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