KEGG   PATHWAY: rro05410
Entry
rro05410                    Pathway                                

Name
Hypertrophic cardiomyopathy - Rhinopithecus roxellana (golden snub-nosed monkey)
Description
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myfibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in the genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myfilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction.
Class
Human Diseases; Cardiovascular disease
Pathway map
rro05410  Hypertrophic cardiomyopathy
rro05410

Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104680210  ITGA1; integrin alpha-1 isoform X1 [KO:K06480]
104672477  ITGA2; integrin alpha-2 [KO:K06481]
104654717  ITGA2B; integrin alpha-IIb [KO:K06476]
104680261  ITGA3; integrin alpha-3 [KO:K06482]
104666588  ITGA4; integrin alpha-4 [KO:K06483]
104670562  ITGA5; integrin alpha-5 [KO:K06484]
104673514  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
104673715  ITGA7; integrin alpha-7 isoform X1 [KO:K06583]
104664159  ITGA8; integrin alpha-8 isoform X1 [KO:K06584]
104672775  ITGA9; integrin alpha-9 [KO:K06585]
104671046  ITGA10; integrin alpha-10 isoform X1 [KO:K06586]
104662593  ITGA11; integrin alpha-11 [KO:K06587]
104667754  ITGAV; integrin alpha-V isoform X2 [KO:K06487]
104663301  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
104662513  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
104681299  ITGB4; integrin beta-4 isoform X4 [KO:K06525]
104655400  ITGB5; integrin beta-5 [KO:K06588]
104674711  ITGB6; integrin beta-6 isoform X1 [KO:K06589]
104670606  ITGB7; integrin beta-7 isoform X1 [KO:K06590]
104658643  ITGB8; integrin beta-8 [KO:K06591]
104657298  SGCD; delta-sarcoglycan isoform X1 [KO:K12563]
104675145  SGCG; gamma-sarcoglycan isoform X1 [KO:K12564]
104680269  SGCA; alpha-sarcoglycan isoform X1 [KO:K12565]
104678338  SGCB; beta-sarcoglycan [KO:K12566]
104670221  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
104655298  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
104667323  DAG1; dystroglycan [KO:K06265]
104660062  DES; desmin [KO:K07610]
104654953  ACTG1; actin, cytoplasmic 2 [KO:K05692]
104665228  ACTB; actin, cytoplasmic 1 [KO:K05692]
104677536  LOW QUALITY PROTEIN: titin [KO:K12567] [EC:2.7.11.1]
104677716  titin-like [KO:K12567] [EC:2.7.11.1]
104661875  TNNT2; troponin T, cardiac muscle isoform X11 [KO:K12045]
104663703  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
104674758  TNNI3; troponin I, cardiac muscle [KO:K12044]
104665644  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
104670859  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
104672471  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
104663504  TPM3; tropomyosin alpha-3 chain isoform X5 [KO:K09290]
104677298  tropomyosin alpha-3 chain-like isoform X1 [KO:K09290]
115898675  tropomyosin alpha-3 chain-like isoform X1 [KO:K09290]
104661006  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
104668410  MYBPC3; myosin-binding protein C, cardiac-type [KO:K12568]
104671315  MYL3; myosin light chain 3 [KO:K12749]
104674641  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
104674161  myosin-6 [KO:K17751]
104664872  myosin-7 [KO:K17751]
104663542  EMD; emerin [KO:K12569]
104682784  emerin [KO:K12569]
104664914  LMNA; lamin [KO:K12641]
104659017  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
104672388  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
104661816  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X5 [KO:K04853]
104661868  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
104674863  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X4 [KO:K04862]
104662886  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X2 [KO:K04863]
104679736  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X2 [KO:K04864]
104669805  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
104681577  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
104667936  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
104662214  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
104662537  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
104675426  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
104682573  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
104665906  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
104675491  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
104675427  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
104676025  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
104676026  CACNG7; voltage-dependent calcium channel gamma-7 subunit isoform X1 [KO:K04872]
104676051  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
104679189  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
104682143  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
104677250  ATP2A3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
104674813  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X3 [KO:K05853] [EC:7.2.2.10]
104676941  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.11]
104664292  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.11]
104678672  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
104666241  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
104660035  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200]
104679727  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
104678710  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X3 [KO:K07200]
104675473  angiotensin-converting enzyme isoform X1 [KO:K01283] [EC:3.4.15.1]
104675505  LOW QUALITY PROTEIN: angiotensin-converting enzyme-like protein Ace3 [KO:K01283] [EC:3.4.15.1]
104657459  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
104676086  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
104662252  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
104677599  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
104661913  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104675233  IL6; interleukin-6 isoform X1 [KO:K05405]
104657358  EDN1; endothelin-1 [KO:K16366]
104670705  AGT; angiotensinogen [KO:K09821]
104659649  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
104663033  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
104673384  SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849]
Compound
C00002  ATP
C00076  Calcium cation
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
Moolman-Smook JC, Mayosi BM, Brink PA, Corfield VA
  Title
Molecular genetics of cardiomyopathy: changing times, shifting paradigms.
  Journal
Cardiovasc J S Afr 14:145-55 (2003)
Reference
  Authors
Taylor MR, Carniel E, Mestroni L
  Title
Familial hypertrophic cardiomyopathy: clinical features, molecular genetics and molecular genetic testing.
  Journal
Expert Rev Mol Diagn 4:99-113 (2004)
DOI:10.1586/14737159.4.1.99
Reference
  Authors
Marian AJ
  Title
Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy.
  Journal
Lancet 355:58-60 (2000)
DOI:10.1016/S0140-6736(99)06187-5
Reference
  Authors
Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H
  Title
Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis.
  Journal
Hum Mol Genet 10:1215-20 (2001)
DOI:10.1093/hmg/10.11.1215
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
Morimoto S
  Title
Sarcomeric proteins and inherited cardiomyopathies.
  Journal
Cardiovasc Res 77:659-66 (2008)
DOI:10.1093/cvr/cvm084
Reference
  Authors
Cambronero F, Marin F, Roldan V, Hernandez-Romero D, Valdes M, Lip GY
  Title
Biomarkers of pathophysiology in hypertrophic cardiomyopathy: implications for clinical management and prognosis.
  Journal
Eur Heart J 30:139-51 (2009)
DOI:10.1093/eurheartj/ehn538
Reference
  Authors
Towbin JA, Bowles NE
  Title
The failing heart.
  Journal
Nature 415:227-33 (2002)
DOI:10.1038/415227a
Reference
  Authors
Sorajja P, Elliott PM, McKenna WJ
  Title
The molecular genetics of hypertrophic cardiomyopathy: prognostic implications.
  Journal
Europace 2:4-14 (2000)
DOI:10.1053/eupc.1999.0067
Reference
  Authors
Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, Ommen SR, Potter JD, Ackerman MJ
  Title
Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C.
  Journal
J Mol Cell Cardiol 45:281-8 (2008)
DOI:10.1016/j.yjmcc.2008.05.003
Related
pathway
rro04260  Cardiac muscle contraction
rro04350  TGF-beta signaling pathway
rro04512  ECM-receptor interaction
rro04614  Renin-angiotensin system
rro04630  JAK-STAT signaling pathway
KO pathway
ko05410   
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