Entry
Name
Hypertrophic cardiomyopathy - Macaca mulatta (rhesus 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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Macaca mulatta (rhesus monkey) [GN:
mcc ]
Gene
722472 LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637 ]
715394 LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637 ]
697047 TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865 ]
698470 TNNI3; troponin I, cardiac muscle isoform X2 [KO:K12044 ]
705236 TPM1; tropomyosin alpha-1 chain isoform X8 [KO:K10373 ]
719428 TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375 ]
712093 MYBPC3; myosin-binding protein C, cardiac-type isoform X1 [KO:K12568 ]
711937 MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
721721 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X13 [KO:K04850 ]
693924 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
715787 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
708706 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
695864 CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X2 [KO:K04862 ]
701226 CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863 ]
708091 CACNB3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864 ]
695172 CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865 ]
708215 CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858 ]
702429 CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X7 [KO:K04859 ]
693356 CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860 ]
721703 CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861 ]
718591 CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866 ]
696294 CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867 ]
701324 CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868 ]
718540 CACNG4; voltage-dependent calcium channel gamma-4 subunit isoform X2 [KO:K04869 ]
718465 CACNG5; voltage-dependent calcium channel gamma-5 subunit isoform X1 [KO:K04870 ]
720548 CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871 ]
720271 CACNG7; voltage-dependent calcium channel gamma-7 subunit isoform X1 [KO:K04872 ]
106994852 CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873 ]
707768 ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X3 [KO:K05853 ] [EC:7.2.2.10 ]
708058 ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853 ] [EC:7.2.2.10 ]
710702 ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X3 [KO:K05853 ] [EC:7.2.2.10 ]
695558 PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198 ] [EC:2.7.11.31 ]
695737 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
699806 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
702782 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200 ]
709298 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
100425255 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
698444 IGF1; insulin-like growth factor I precursor [KO:K05459 ]
106992315 TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375 ]
707540 TGFB2; transforming growth factor beta-2 precursor [KO:K13376 ]
703239 TGFB3; transforming growth factor beta-3 precursor [KO:K13377 ]
718243 SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849 ]
574193 SLC8A1; sodium/calcium exchanger 1 precursor [KO:K05849 ]
713061 SLC8A3; sodium/calcium exchanger 3 isoform X2 [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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