KEGG   PATHWAY: ptr05414
Entry
ptr05414                    Pathway                                
Name
Dilated cardiomyopathy - Pan troglodytes (chimpanzee)
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
ptr05414  Dilated cardiomyopathy
ptr05414

Organism
Pan troglodytes (chimpanzee) [GN:ptr]
Gene
461880  ITGA1; integrin alpha-1 [KO:K06480]
471550  ITGA2; integrin alpha-2 isoform X3 [KO:K06481]
454730  ITGA2B; integrin alpha-IIb isoform X1 [KO:K06476]
455111  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
470596  ITGA4; integrin alpha-4 isoform X1 [KO:K06483]
451958  ITGA5; integrin alpha-5 isoform X1 [KO:K06484]
459742  ITGA6; integrin alpha-6 isoform X6 [KO:K06485]
451967  ITGA7; integrin alpha-7 isoform X4 [KO:K06583]
450323  ITGA8; integrin alpha-8 isoform X2 [KO:K06584]
470789  ITGA9; integrin alpha-9 [KO:K06585]
457982  ITGA10; integrin alpha-10 isoform X2 [KO:K06586]
453537  ITGA11; integrin alpha-11 [KO:K06587]
459807  ITGAV; integrin alpha-V isoform X2 [KO:K06487]
450396  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
468295  ITGB3; integrin beta-3 isoform X2 [KO:K06493]
454887  ITGB4; integrin beta-4 isoform X1 [KO:K06525]
460646  ITGB5; integrin beta-5 [KO:K06588]
459683  ITGB6; integrin beta-6 isoform X1 [KO:K06589]
451934  ITGB7; integrin beta-7 isoform X1 [KO:K06590]
463282  ITGB8; integrin beta-8 isoform X1 [KO:K06591]
739128  SSPN; sarcospan isoform X1 [KO:K22194]
468403  SGCA; alpha-sarcoglycan [KO:K12565]
461332  SGCB; beta-sarcoglycan isoform X2 [KO:K12566]
745014  SGCG; gamma-sarcoglycan isoform X2 [KO:K12564]
462216  SGCD; delta-sarcoglycan isoform X1 [KO:K12563]
463544  SGCE; epsilon-sarcoglycan isoform X6 [KO:K27061]
472703  SGCZ; zeta-sarcoglycan [KO:K27062]
455302  LAMA1; laminin subunit alpha-1 isoform X2 [KO:K05637]
472122  LAMA2; laminin subunit alpha-2 isoform X5 [KO:K05637]
460372  DAG1; dystroglycan [KO:K06265]
738786  CAV3; caveolin-3 [KO:K12959]
467139  NOS1; nitric oxide synthase, brain isoform X2 [KO:K13240] [EC:1.14.13.39]
458181  SNTA1; alpha-1-syntrophin isoform X1 [KO:K24063]
107966376  SNTB2; beta-2-syntrophin [KO:K24064]
464362  SNTB1; beta-1-syntrophin isoform X2 [KO:K24064]
455367  DTNA; dystrobrevin alpha isoform X19 [KO:K26998]
465559  DMD; dystrophin isoform X1 [KO:K10366]
470657  DES; desmin [KO:K07610]
746570  ACTG1; actin, cytoplasmic 2 [KO:K05692]
450133  ACTB; actin, cytoplasmic 1 [KO:K05692]
459784  TTN; titin [KO:K12567] [EC:2.7.11.1]
457618  TNNT2; troponin T, cardiac muscle isoform X5 [KO:K12045]
746369  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
735514  TNNI3; troponin I, cardiac muscle [KO:K12044]
453307  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
453495  TPM1; tropomyosin alpha-1 chain isoform X7 [KO:K10373]
465078  TPM2; tropomyosin beta chain isoform X4 [KO:K10374]
458000  TPM3; tropomyosin alpha-3 chain isoform X18 [KO:K09290]
470670  tropomyosin alpha-3 chain-like isoform X2 [KO:K09290]
100612873  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
451168  MYBPC3; myosin-binding protein C, cardiac-type isoform X1 [KO:K12568]
460327  MYL3; myosin light chain 3 [KO:K12749]
452243  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
452801  MYH6; myosin-6 [KO:K17751]
745215  MYH7; myosin-7 [KO:K17751]
465938  EMD; emerin [KO:K12569]
457385  LMNA; lamin [KO:K12641]
100608894  immunoglobulin heavy variable 3-23 [KO:K06856]
104002202  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
104002200  immunoglobulin heavy variable 6-1 [KO:K06856]
466206  ADRB1; beta-1 adrenergic receptor [KO:K04141]
469986  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X5 [KO:K04632]
104003639  neuroendocrine secretory protein 55 [KO:K04632]
463392  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100608010  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
459070  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
452819  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
470905  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
451866  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
473278  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
464400  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
453869  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
469367  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X11 [KO:K04345] [EC:2.7.11.11]
472944  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
107966260  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
466915  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
460447  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
740711  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
469635  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
454624  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
740138  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
451867  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
459660  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X3 [KO:K04865]
463504  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X7 [KO:K04858]
460396  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
460457  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
466912  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X8 [KO:K04861]
741106  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
458799  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
746707  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
741406  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
100609964  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
749208  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
749196  CACNG7; voltage-dependent calcium channel gamma-7 subunit isoform X1 [KO:K04872]
457846  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
454019  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
100613278  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
452231  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X2 [KO:K05853] [EC:7.2.2.10]
100613044  PLN; cardiac phospholamban [KO:K05852]
468932  SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849]
470358  SLC8A1; sodium/calcium exchanger 1 isoform X12 [KO:K05849]
467491  SLC8A3; sodium/calcium exchanger 3 isoform X2 [KO:K05849]
741055  IGF1; insulin-like growth factor I isoform X6 [KO:K05459]
456060  TGFB1; transforming growth factor beta-1 isoform X2 [KO:K13375]
457742  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
453054  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
494186  TNF; tumor necrosis factor [KO:K03156]
450104  AGT; angiotensinogen precursor [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
ptr04260  Cardiac muscle contraction
ptr04350  TGF-beta signaling pathway
ptr04512  ECM-receptor interaction
ptr04614  Renin-angiotensin system
ptr05416  Viral myocarditis
KO pathway
ko05414   
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