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Entry
ko05410                     Pathway                                

Name
Hypertrophic cardiomyopathy (HCM)
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 diseases
BRITE hierarchy
Pathway map
Hypertrophic cardiomyopathy (HCM)
ko05410

All organismsOrtholog table
Disease
H00292  
Hypertrophic cardiomyopathy (HCM)
H00728  
Brugada syndrome (BRS)
H01154  
Wolff-Parkinson-White (WPW) syndrome
Orthology
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
K06265  
dystroglycan 1
K07610  
desmin
K10366  
dystrophin
K05692  
actin beta/gamma 1
K12567  
titin [EC:2.7.11.1]
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
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
K07198  
5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.11]
K07199  
5'-AMP-activated protein kinase, regulatory beta subunit
K07200  
5'-AMP-activated protein kinase, regulatory gamma subunit
K01283  
peptidyl-dipeptidase A [EC:3.4.15.1]
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
Compound
C00002  
ATP
C00076  
Calcium cation
C01330  
Sodium cation
C02135  
Angiotensin II
C16010  
Endothelin-1
Reference
  Authors
Fatkin D, Graham RM
  Title
Molecular mechanisms of inherited cardiomyopathies.
  Journal
Physiol Rev 82:945-80 (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)
Reference
  Authors
Tei C (ed).
  Title
[Up to date of basic and clinical aspects of cardiomyopathies] (In Japanese)
  Journal
Ishiyakushupan (2009)
Reference
  Authors
Marian AJ
  Title
Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy.
  Journal
Lancet 355:58-60 (2000)
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)
Reference
  Authors
Franz WM, Muller OJ, Katus HA
  Title
Cardiomyopathies: from genetics to the prospect of treatment.
  Journal
Lancet 358:1627-37 (2001)
Reference
  Authors
Morimoto S
  Title
Sarcomeric proteins and inherited cardiomyopathies.
  Journal
Cardiovasc Res 77:659-66 (2008)
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)
Reference
  Authors
Towbin JA, Bowles NE
  Title
The failing heart.
  Journal
Nature 415:227-33 (2002)
Reference
  Authors
Sorajja P, Elliott PM, McKenna WJ
  Title
The molecular genetics of hypertrophic cardiomyopathy: prognostic implications.
  Journal
Europace 2:4-14 (2000)
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)

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