KEGG   PATHWAY: pleu05414
Entry
pleu05414                   Pathway                                
Name
Dilated cardiomyopathy - Peromyscus leucopus (white-footed mouse)
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
pleu05414  Dilated cardiomyopathy
pleu05414

Disease
H00294  Dilated cardiomyopathy
Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680598  Actg1; LOW QUALITY PROTEIN: actin, cytoplasmic 2 [KO:K05692]
114680916  Itga10; LOW QUALITY PROTEIN: integrin alpha-10 [KO:K06586]
114681419  Slc8a2; sodium/calcium exchanger 2 [KO:K05849]
114681739  Itga7; integrin alpha-7 isoform X9 [KO:K06583]
114682025  [KO:K04632]
114682029  [KO:K04632]
114682499  Itga9; integrin alpha-9 [KO:K06585]
114683299  Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
114683427  Sntb2; beta-2-syntrophin [KO:K24064]
114684152  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114684256  [KO:K05692]
114684973  Sgcb; beta-sarcoglycan [KO:K12566]
114685054  Ryr2; LOW QUALITY PROTEIN: ryanodine receptor 2 [KO:K04962]
114685302  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
114685849  [KO:K10375]
114686117  Slc8a1; LOW QUALITY PROTEIN: sodium/calcium exchanger 1 [KO:K05849]
114686204  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114686672  Atp2a1; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
114687339  Cacna2d1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X3 [KO:K04858]
114687520  Cacng8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
114687522  Cacng7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
114687528  Cacng6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
114689156  Tnni3; troponin I, cardiac muscle [KO:K12044]
114689585  Cav3; caveolin-3 [KO:K12959]
114690437  Cacng4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
114690438  Cacng5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
114690478  Cacng1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
114690977  Tpm1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
114691660  Itga11; integrin alpha-11 [KO:K06587]
114692206  Cacng3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
114692435  Itgb6; integrin beta-6 isoform X1 [KO:K06589]
114692898  Sgca; alpha-sarcoglycan [KO:K12565]
114692904  Itga3; integrin alpha-3 isoform X1 [KO:K06482]
114693446  Sgce; epsilon-sarcoglycan isoform X1 [KO:K27061]
114693822  Sgcg; gamma-sarcoglycan [KO:K12564]
114693931  Cacnb2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
114693946  Itga8; LOW QUALITY PROTEIN: integrin alpha-8 [KO:K06584]
114693962  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114694084  [KO:K05853] [EC:7.2.2.10]
114694218  Cacng2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
114694831  Sntb1; beta-1-syntrophin [KO:K24064]
114695158  Sgcz; zeta-sarcoglycan [KO:K27062]
114696121  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
114696602  Itga5; integrin alpha-5 [KO:K06484]
114696632  Itgb7; integrin beta-7 isoform X1 [KO:K06590]
114697069  Adrb1; beta-1 adrenergic receptor [KO:K04141]
114697107  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
114697505  Actc1; actin, alpha cardiac muscle 1 [KO:K12314]
114697724  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114697904  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
114698133  Tnnt2; troponin T, cardiac muscle [KO:K12045]
114698210  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
114698264  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114698446  Cacnb4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
114698613  Lama2; laminin subunit alpha-2 isoform X1 [KO:K05637]
114698733  Slc8a3; LOW QUALITY PROTEIN: sodium/calcium exchanger 3 [KO:K05849]
114699651  Nos1; nitric oxide synthase, brain isoform X2 [KO:K13240] [EC:1.14.13.39]
114699683  Mybpc3; myosin-binding protein C, cardiac-type [KO:K12568]
114700619  Igf1; insulin-like growth factor I isoform X2 [KO:K05459]
114700759  Cacna2d4; voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X1 [KO:K04861]
114700762  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X8 [KO:K04850]
114700805  Ttn; LOW QUALITY PROTEIN: titin [KO:K12567] [EC:2.7.11.1]
114701036  Itgb8; integrin beta-8 [KO:K06591]
114701281  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
114701667  Dmd; dystrophin isoform X2 [KO:K10366]
114702139  Cacna2d3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
114702233  Itga2b; LOW QUALITY PROTEIN: integrin alpha-IIb [KO:K06476]
114702284  Itgb3; integrin beta-3 [KO:K06493]
114703016  Itga2; LOW QUALITY PROTEIN: integrin alpha-2 [KO:K06481]
114703209  Tpm2; tropomyosin beta chain isoform X4 [KO:K10374]
114703598  Itgav; integrin alpha-V isoform X1 [KO:K06487]
114703730  Itga4; integrin alpha-4 [KO:K06483]
114703745  Itga1; integrin alpha-1 [KO:K06480]
114704074  Lama1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
114704479  Itga6; LOW QUALITY PROTEIN: integrin alpha-6 [KO:K06485]
114704560  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
114704572  [KO:K10351]
114704841  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114704849  Itgb5; LOW QUALITY PROTEIN: integrin beta-5 [KO:K06588]
114705218  Dag1; dystroglycan [KO:K06265]
114705242  Myl3; myosin light chain 3 [KO:K12749]
114705499  Actb; actin, cytoplasmic 1 [KO:K05692]
114705682  Dtna; dystrobrevin alpha isoform X3 [KO:K26998]
114705780  Itgb1; integrin beta-1 isoform X1 [KO:K05719]
114705817  Tnf; tumor necrosis factor [KO:K03156]
114706254  Emd; emerin [KO:K12569]
114706333  Atp2a3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
114706377  Sgcd; delta-sarcoglycan [KO:K12563]
114706518  Snta1; alpha-1-syntrophin [KO:K24063]
114706913  Cacnb1; voltage-dependent L-type calcium channel subunit beta-1 isoform X3 [KO:K04862]
114707063  Itgb4; integrin beta-4 isoform X2 [KO:K06525]
114707150  Agt; angiotensinogen [KO:K09821]
114707877  Tpm3; tropomyosin alpha-3 chain isoform X12 [KO:K09290]
114708193  Tnnc1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
114708394  Sspn; sarcospan isoform X1 [KO:K22194]
114708501  Adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
114708522  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
114708536  Cacnb3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
114708688  [KO:K17751]
114708693  [KO:K17751]
114708701  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114709309  Des; desmin [KO:K07610]
114709571  Tpm4; tropomyosin alpha-4 chain isoform X2 [KO:K10375]
114710615  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
114710697  Pln; cardiac phospholamban [KO:K05852]
114710954  Cacna2d2; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
119087871  [KO:K04962]
119087872  [KO:K04962]
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
pleu04260  Cardiac muscle contraction
pleu04350  TGF-beta signaling pathway
pleu04512  ECM-receptor interaction
pleu04614  Renin-angiotensin system
pleu05416  Viral myocarditis
KO pathway
ko05414   

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