Entry
Name
Hypertrophic cardiomyopathy - Rattus norvegicus (rat)
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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Rattus norvegicus (rat) [GN:
rno ]
Gene
296456 Itgav; integrin alpha-V isoform 1 precursor [KO:K06487 ]
303468 Sgca; alpha-sarcoglycan isoform 1 precursor [KO:K12565 ]
24837 Tnnt2; troponin T, cardiac muscle isoform 1 [KO:K12045 ]
290561 Tnnc1; troponin C, slow skeletal and cardiac muscles [KO:K05865 ]
24851 Tpm1; tropomyosin alpha-1 chain isoform Tpm1.6cy [KO:K10373 ]
500450 Tpm2; tropomyosin beta chain isoform Tpm2.1sm/cy [KO:K10374 ]
117557 Tpm3; tropomyosin alpha-3 chain isoform Tpm3.3cy [KO:K09290 ]
295929 Mybpc3; myosin-binding protein C, cardiac-type [KO:K12568 ]
363925 Myl2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
24239 Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
29716 Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
114493 Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
682930 Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
50688 Cacnb1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862 ]
116600 Cacnb2; voltage-dependent L-type calcium channel subunit beta-2 isoform 2 [KO:K04863 ]
25297 Cacnb3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864 ]
58942 Cacnb4; voltage-dependent L-type calcium channel subunit beta-4 isoform 2 [KO:K04865 ]
25399 Cacna2d1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform 3 precursor [KO:K04858 ]
300992 Cacna2d2; voltage-dependent calcium channel subunit alpha-2/delta-2 precursor [KO:K04859 ]
306243 Cacna2d3; voltage-dependent calcium channel subunit alpha-2/delta-3 precursor [KO:K04860 ]
312668 Cacna2d4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861 ]
29658 Cacng1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866 ]
84347 Cacng2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867 ]
140724 Cacng3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868 ]
140725 Cacng4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869 ]
140726 Cacng5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870 ]
140727 Cacng6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871 ]
140728 Cacng7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872 ]
140729 Cacng8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873 ]
29693 Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b [KO:K05853 ] [EC:7.2.2.10 ]
83803 Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
64562 Prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
25520 Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
301518 Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
498012 Ace3; angiotensin I converting enzyme (peptidyl-dipeptidase A) 3 precursor [KO:K01283 ] [EC:3.4.15.1 ]
24482 Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459 ]
59086 Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375 ]
81809 Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376 ]
25717 Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377 ]
29715 Slc8a1; sodium/calcium exchanger 1 isoform 6 precursor [KO:K05849 ]
140447 Slc8a2; sodium/calcium exchanger 2 precursor [KO:K05849 ]
140448 Slc8a3; sodium/calcium exchanger 3 precursor [KO:K05849 ]
Compound
Reference
Authors
Fatkin D, Graham RM
Title
Molecular mechanisms of inherited cardiomyopathies.
Journal
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
Reference
Authors
Marian AJ
Title
Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy.
Journal
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
Reference
Authors
Franz WM, Muller OJ, Katus HA
Title
Cardiomyopathies: from genetics to the prospect of treatment.
Journal
Reference
Authors
Morimoto S
Title
Sarcomeric proteins and inherited cardiomyopathies.
Journal
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
Reference
Authors
Towbin JA, Bowles NE
Title
The failing heart.
Journal
Reference
Authors
Sorajja P, Elliott PM, McKenna WJ
Title
The molecular genetics of hypertrophic cardiomyopathy: prognostic implications.
Journal
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
Related pathway
KO pathway
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