KEGG   PATHWAY: ko05410
ko05410                     Pathway                                

Hypertrophic cardiomyopathy
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.
Human Diseases; Cardiovascular disease
Pathway map
ko05410  Hypertrophic cardiomyopathy

H00292  Hypertrophic cardiomyopathy
K06480  integrin alpha 1
K06481  integrin alpha 2
K06476  integrin alpha 2B
K06482  integrin alpha 3
K06483  integrin alpha 4
K06484  integrin alpha 5
K06485  integrin alpha 6
K06583  integrin alpha 7
K06584  integrin alpha 8
K06585  integrin alpha 9
K06586  integrin alpha 10
K06587  integrin alpha 11
K06487  integrin alpha V
K05719  integrin beta 1
K06493  integrin beta 3
K06525  integrin beta 4
K06588  integrin beta 5
K06589  integrin beta 6
K06590  integrin beta 7
K06591  integrin beta 8
K12563  delta-sarcoglycan
K12564  gamma-sarcoglycan
K12565  alpha-sarcoglycan
K12566  beta-sarcoglycan
K05637  laminin, alpha 1/2
K06265  dystroglycan 1
K07610  desmin
K10366  dystrophin
K05692  actin beta/gamma 1
K12567  titin [EC:]
K12045  troponin T, cardiac muscle
K05865  troponin C, slow skeletal and cardiac muscles
K12044  troponin I, cardiac muscle
K12314  actin, alpha cardiac muscle
K10373  tropomyosin 1
K10374  tropomyosin 2
K09290  tropomyosin 3
K10375  tropomyosin 4
K12568  myosin-binding protein C, cardiac-type
K12749  myosin light chain 3
K10351  myosin regulatory light chain 2
K17751  myosin heavy chain 6/7
K12569  emerin
K12641  lamin A/C
K04850  voltage-dependent calcium channel L type alpha-1C
K04851  voltage-dependent calcium channel L type alpha-1D
K04853  voltage-dependent calcium channel L type alpha-1F
K04857  voltage-dependent calcium channel L type alpha-1S
K04862  voltage-dependent calcium channel beta-1
K04863  voltage-dependent calcium channel beta-2
K04864  voltage-dependent calcium channel beta-3
K04865  voltage-dependent calcium channel beta-4
K04858  voltage-dependent calcium channel alpha-2/delta-1
K04859  voltage-dependent calcium channel alpha-2/delta-2
K04860  voltage-dependent calcium channel alpha-2/delta-3
K04861  voltage-dependent calcium channel alpha-2/delta-4
K04866  voltage-dependent calcium channel gamma-1
K04867  voltage-dependent calcium channel gamma-2
K04868  voltage-dependent calcium channel gamma-3
K04869  voltage-dependent calcium channel gamma-4
K04870  voltage-dependent calcium channel gamma-5
K04871  voltage-dependent calcium channel gamma-6
K04872  voltage-dependent calcium channel gamma-7
K04873  voltage-dependent calcium channel gamma-8
K04962  ryanodine receptor 2
K05853  P-type Ca2+ transporter type 2A [EC:]
K07198  5'-AMP-activated protein kinase, catalytic alpha subunit [EC:]
K07199  5'-AMP-activated protein kinase, regulatory beta subunit
K07200  5'-AMP-activated protein kinase, regulatory gamma subunit
K01283  peptidyl-dipeptidase A [EC:]
K05459  insulin-like growth factor 1
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K03156  tumor necrosis factor superfamily, member 2
K05405  interleukin 6
K16366  endothelin-1
K09821  angiotensinogen
K05849  solute carrier family 8 (sodium/calcium exchanger)
C00002  ATP
C00076  Calcium cation
C01330  Sodium cation
Fatkin D, Graham RM
Molecular mechanisms of inherited cardiomyopathies.
Physiol Rev 82:945-80 (2002)
Moolman-Smook JC, Mayosi BM, Brink PA, Corfield VA
Molecular genetics of cardiomyopathy: changing times, shifting paradigms.
Cardiovasc J S Afr 14:145-55 (2003)
Taylor MR, Carniel E, Mestroni L
Familial hypertrophic cardiomyopathy: clinical features, molecular genetics and molecular genetic testing.
Expert Rev Mol Diagn 4:99-113 (2004)
Marian AJ
Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy.
Lancet 355:58-60 (2000)
Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H
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.
Hum Mol Genet 10:1215-20 (2001)
Franz WM, Muller OJ, Katus HA
Cardiomyopathies: from genetics to the prospect of treatment.
Lancet 358:1627-37 (2001)
Morimoto S
Sarcomeric proteins and inherited cardiomyopathies.
Cardiovasc Res 77:659-66 (2008)
Cambronero F, Marin F, Roldan V, Hernandez-Romero D, Valdes M, Lip GY
Biomarkers of pathophysiology in hypertrophic cardiomyopathy: implications for clinical management and prognosis.
Eur Heart J 30:139-51 (2009)
Towbin JA, Bowles NE
The failing heart.
Nature 415:227-33 (2002)
Sorajja P, Elliott PM, McKenna WJ
The molecular genetics of hypertrophic cardiomyopathy: prognostic implications.
Europace 2:4-14 (2000)
Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, Ommen SR, Potter JD, Ackerman MJ
Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C.
J Mol Cell Cardiol 45:281-8 (2008)
ko04260  Cardiac muscle contraction
ko04350  TGF-beta signaling pathway
ko04512  ECM-receptor interaction
ko04614  Renin-angiotensin system
ko04630  JAK-STAT signaling pathway

DBGET integrated database retrieval system