KEGG   PATHWAY: ocu05412
Entry
ocu05412                    Pathway                                
Name
Arrhythmogenic right ventricular cardiomyopathy - Oryctolagus cuniculus (rabbit)
Description
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVC. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.
Class
Human Diseases; Cardiovascular disease
Pathway map
ocu05412  Arrhythmogenic right ventricular cardiomyopathy
ocu05412

Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100342711  integrin alpha-1 [KO:K06480]
100101621  integrin alpha-2 [KO:K06481]
100008734  ITGA2B; integrin alpha-IIb precursor [KO:K06476]
100348594  integrin alpha-3 [KO:K06482]
100346103  integrin alpha-4 isoform X1 [KO:K06483]
100009172  integrin alpha-5 [KO:K06484]
100008642  integrin alpha-6 isoform X1 [KO:K06485]
100346005  integrin alpha-7 isoform X6 [KO:K06583]
127487418  integrin alpha-7 isoform X1 [KO:K06583]
100351181  integrin alpha-8 [KO:K06584]
100339625  integrin alpha-9 [KO:K06585]
103350383  integrin alpha-9 [KO:K06585]
100340248  integrin alpha-10 isoform X1 [KO:K06586]
100344251  integrin alpha-11 [KO:K06587]
100008956  integrin alpha-V isoform X1 [KO:K06487]
100008898  integrin beta-1 isoform X2 [KO:K05719]
100008735  ITGB3; integrin beta-3 precursor [KO:K06493]
100101587  LOW QUALITY PROTEIN: integrin beta-4 [KO:K06525]
100353546  integrin beta-5 [KO:K06588]
100338232  integrin beta-6 isoform X1 [KO:K06589]
100350557  integrin beta-7 isoform X1 [KO:K06590]
100009141  ITGB8; integrin beta-8 precursor [KO:K06591]
100008714  SSPN; sarcospan [KO:K22194]
100009178  SGCA; alpha-sarcoglycan precursor [KO:K12565]
100009208  SGCB; beta-sarcoglycan [KO:K12566]
100009214  SGCG; gamma-sarcoglycan [KO:K12564]
100351233  delta-sarcoglycan [KO:K12563]
100352334  epsilon-sarcoglycan isoform X3 [KO:K27061]
100349537  zeta-sarcoglycan [KO:K27062]
100350500  laminin subunit alpha-2 isoform X1 [KO:K05637]
100357482  laminin subunit alpha-1 isoform X1 [KO:K05637]
100009278  DAG1; dystroglycan 1 precursor [KO:K06265]
100342999  caveolin-3 [KO:K12959]
100009243  NOS1; nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
100009179  SNTA1; alpha-1-syntrophin [KO:K24063]
103348511  beta-2-syntrophin isoform X1 [KO:K24064]
100354514  beta-1-syntrophin [KO:K24064]
100351412  dystrobrevin alpha isoform X1 [KO:K26998]
100355731  dystrophin isoform X1 [KO:K10366]
100328890  DES; desmin [KO:K07610]
100008822  actin, cytoplasmic 1 [KO:K05692]
100009272  ACTB; actin, cytoplasmic 1 [KO:K05692]
100341037  LOW QUALITY PROTEIN: actin, cytoplasmic 2-like [KO:K05692]
100328755  EMD; emerin [KO:K12569]
100343574  lamin isoform X1 [KO:K12641]
100125985  catenin beta-1 [KO:K02105]
100339216  transcription factor 7 isoform X1 [KO:K02620]
100340471  transcription factor 7-like 1 isoform X1 [KO:K04490]
100358378  transcription factor 7-like 2 isoform X1 [KO:K04491]
100352691  lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100101555  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
100327259  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100357261  voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100009585  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100009109  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
100009277  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
100009402  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864]
100344224  voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
100009105  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 preproprotein [KO:K04858]
100340494  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X7 [KO:K04859]
100351327  voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
100354108  voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
100009263  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
100350483  voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
100350075  voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
100338772  voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
100339021  voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
100351877  voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
100328774  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
103346112  voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
100009536  RYR2; ryanodine receptor 2 [KO:K04962]
100037716  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
100354976  sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X2 [KO:K05853] [EC:7.2.2.10]
100038308  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
100339605  sodium/calcium exchanger 3 isoform X1 [KO:K05849]
100328570  SLC8A1; sodium/calcium exchanger 1 precursor [KO:K05849]
100358483  sodium/calcium exchanger 2 [KO:K05849]
100344571  cadherin-2 [KO:K06736]
100345709  junction plakoglobin [KO:K10056]
100343241  catenin alpha-3 isoform X1 [KO:K05691]
100328952  CTNNA1; catenin alpha-1 [KO:K05691]
100352391  catenin alpha-2 isoform X1 [KO:K05691]
100009544  alpha-actinin-3 isoform X2 [KO:K21073]
100350274  alpha-actinin-2 [KO:K21073]
100344572  desmocollin-2 isoform X1 [KO:K07601]
100347738  plakophilin-2 isoform X1 [KO:K12642]
100354434  desmoplakin isoform X1 [KO:K10381]
100348149  desmoglein-2 [KO:K07597]
100008935  GJA1; gap junction alpha-1 protein [KO:K07372]
Compound
C00076  Calcium cation
C01330  Sodium cation
Reference
  Authors
Herren T, Gerber PA, Duru F
  Title
Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare "disease of the desmosome" with multiple clinical presentations.
  Journal
Clin Res Cardiol 98:141-58 (2009)
DOI:10.1007/s00392-009-0751-4
Reference
  Authors
van Tintelen JP, Hofstra RM, Wiesfeld AC, van den Berg MP, Hauer RN, Jongbloed JD
  Title
Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon?
  Journal
Curr Opin Cardiol 22:185-92 (2007)
DOI:10.1097/HCO.0b013e3280d942c4
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
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
MacRae CA, Birchmeier W, Thierfelder L
  Title
Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism.
  Journal
J Clin Invest 116:1825-8 (2006)
DOI:10.1172/JCI29174
Reference
  Authors
Awad MM, Calkins H, Judge DP
  Title
Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy.
  Journal
Nat Clin Pract Cardiovasc Med 5:258-67 (2008)
DOI:10.1038/ncpcardio1182
Reference
  Authors
Sen-Chowdhry S, Syrris P, McKenna WJ
  Title
Genetics of right ventricular cardiomyopathy.
  Journal
J Cardiovasc Electrophysiol 16:927-35 (2005)
DOI:10.1111/j.1540-8167.2005.40842.x
Reference
  Authors
Ahmad F, Seidman JG, Seidman CE
  Title
The genetic basis for cardiac remodeling.
  Journal
Annu Rev Genomics Hum Genet 6:185-216 (2005)
DOI:10.1146/annurev.genom.6.080604.162132
Related
pathway
ocu04260  Cardiac muscle contraction
ocu04310  Wnt signaling pathway
ocu04512  ECM-receptor interaction
ocu04540  Gap junction
KO pathway
ko05412   
LinkDB

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