KEGG PATHWAY: hsa05414

PATHWAY: hsa05414

Entry

hsa05414 Pathway

Name

Dilated cardiomyopathy - Homo sapiens (human)

Description

Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM ("familial" DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of "familial" DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an "idiopathic" DCM. Current hypotheses regarding causes of "idiopathic" DCM focus on myocarditis induced by enterovirus and subsequent autoimmune myocardium impairments. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with "idiopathic" DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure.

Class

Human Diseases; Cardiovascular diseases

Pathway map

hsa05414

Dilated cardiomyopathy

Disease

H00294	Dilated cardiomyopathy (DCM)
H00728	Brugada syndrome (BRS)

Organism

Homo sapiens (human) [GN:hsa]

Gene

3672	ITGA1; integrin, alpha 1 [KO:K06480]
3673	ITGA2; integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) [KO:K06481]
3674	ITGA2B; integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41) [KO:K06476]
3675	ITGA3; integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor) [KO:K06482]
3676	ITGA4; integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) [KO:K06483]
3678	ITGA5; integrin, alpha 5 (fibronectin receptor, alpha polypeptide) [KO:K06484]
3655	ITGA6; integrin, alpha 6 [KO:K06485]
3679	ITGA7; integrin, alpha 7 [KO:K06583]
8516	ITGA8; integrin, alpha 8 [KO:K06584]
3680	ITGA9; integrin, alpha 9 [KO:K06585]
8515	ITGA10; integrin, alpha 10 [KO:K06586]
101060422	integrin alpha-10-like; K06586 integrin alpha 10 [KO:K06586]
22801	ITGA11; integrin, alpha 11 [KO:K06587]
3685	ITGAV; integrin, alpha V [KO:K06487]
3688	ITGB1; integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) [KO:K05719]
3690	ITGB3; integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) [KO:K06493]
3691	ITGB4; integrin, beta 4 [KO:K06525]
3693	ITGB5; integrin, beta 5 [KO:K06588]
3694	ITGB6; integrin, beta 6 [KO:K06589]
3695	ITGB7; integrin, beta 7 [KO:K06590]
3696	ITGB8; integrin, beta 8 [KO:K06591]
6444	SGCD; sarcoglycan, delta (35kDa dystrophin-associated glycoprotein) [KO:K12563]
6445	SGCG; sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) [KO:K12564]
6442	SGCA; sarcoglycan, alpha (50kDa dystrophin-associated glycoprotein) [KO:K12565]
6443	SGCB; sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) [KO:K12566]
1605	DAG1; dystroglycan 1 (dystrophin-associated glycoprotein 1) [KO:K06265]
1674	DES; desmin [KO:K07610]
1756	DMD; dystrophin [KO:K10366]
60	ACTB; actin, beta [KO:K05692]
71	ACTG1; actin, gamma 1 [KO:K05692]
7273	TTN; titin [KO:K12567] [EC:2.7.11.1]
7139	TNNT2; troponin T type 2 (cardiac) [KO:K12045]
7134	TNNC1; troponin C type 1 (slow) [KO:K05865]
7137	TNNI3; troponin I type 3 (cardiac) [KO:K12044]
70	ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
7168	TPM1; tropomyosin 1 (alpha) [KO:K10373]
7169	TPM2; tropomyosin 2 (beta) [KO:K10374]
7170	TPM3; tropomyosin 3 [KO:K09290]
7171	TPM4; tropomyosin 4 [KO:K10375]
4607	MYBPC3; myosin binding protein C, cardiac [KO:K12568]
4634	MYL3; myosin, light chain 3, alkali [KO:K12749]
4633	MYL2; myosin, light chain 2, regulatory, cardiac, slow [KO:K10351]
2010	EMD; emerin [KO:K12569]
4000	LMNA; lamin A/C [KO:K12641]
153	ADRB1; adrenoceptor beta 1 [KO:K04141]
2778	GNAS; GNAS complex locus [KO:K04632]
107	ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108	ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109	ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883	ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111	ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112	ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113	ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114	ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115	ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566	PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567	PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568	PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613	PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
775	CACNA1C; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
776	CACNA1D; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
778	CACNA1F; calcium channel, voltage-dependent, L type, alpha 1F subunit [KO:K04853]
779	CACNA1S; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
782	CACNB1; calcium channel, voltage-dependent, beta 1 subunit [KO:K04862]
783	CACNB2; calcium channel, voltage-dependent, beta 2 subunit [KO:K04863]
784	CACNB3; calcium channel, voltage-dependent, beta 3 subunit [KO:K04864]
785	CACNB4; calcium channel, voltage-dependent, beta 4 subunit [KO:K04865]
781	CACNA2D1; calcium channel, voltage-dependent, alpha 2/delta subunit 1 [KO:K04858]
9254	CACNA2D2; calcium channel, voltage-dependent, alpha 2/delta subunit 2 [KO:K04859]
55799	CACNA2D3; calcium channel, voltage-dependent, alpha 2/delta subunit 3 [KO:K04860]
93589	CACNA2D4; calcium channel, voltage-dependent, alpha 2/delta subunit 4 [KO:K04861]
786	CACNG1; calcium channel, voltage-dependent, gamma subunit 1 [KO:K04866]
10369	CACNG2; calcium channel, voltage-dependent, gamma subunit 2 [KO:K04867]
10368	CACNG3; calcium channel, voltage-dependent, gamma subunit 3 [KO:K04868]
27092	CACNG4; calcium channel, voltage-dependent, gamma subunit 4 [KO:K04869]
27091	CACNG5; calcium channel, voltage-dependent, gamma subunit 5 [KO:K04870]
59285	CACNG6; calcium channel, voltage-dependent, gamma subunit 6 [KO:K04871]
59284	CACNG7; calcium channel, voltage-dependent, gamma subunit 7 [KO:K04872]
59283	CACNG8; calcium channel, voltage-dependent, gamma subunit 8 [KO:K04873]
6262	RYR2; ryanodine receptor 2 (cardiac) [KO:K04962]
5350	PLN; phospholamban [KO:K05852]
3479	IGF1; insulin-like growth factor 1 (somatomedin C) [KO:K05459]
7040	TGFB1; transforming growth factor, beta 1 [KO:K13375]
7042	TGFB2; transforming growth factor, beta 2 [KO:K13376]
7043	TGFB3; transforming growth factor, beta 3 [KO:K13377]
7124	TNF; tumor necrosis factor [KO:K03156]
3908	LAMA2; laminin, alpha 2 [KO:K05637]
4624	MYH6; myosin, heavy chain 6, cardiac muscle, alpha [KO:K10352]
4625	MYH7; myosin, heavy chain 7, cardiac muscle, beta [KO:K10352]
488	ATP2A2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853] [EC:3.6.3.8]
6546	SLC8A1; solute carrier family 8 (sodium/calcium exchanger), member 1 [KO:K05849]

Compound

C00076	Calcium cation
C00575	3',5'-Cyclic AMP
C01330	Sodium cation
C02135	Angiotensin II

Reference

PMID:12270949

Authors

Fatkin D, Graham RM

Title

Molecular mechanisms of inherited cardiomyopathies.

Journal

Physiol Rev 82:945-80 (2002)

Reference

PMID:18672201

Authors

Lappe JM, Pelfrey CM, Tang WH

Title

Recent insights into the role of autoimmunity in idiopathic dilated cardiomyopathy.

Journal

J Card Fail 14:521-30 (2008)

Reference

PMID:19273156

Authors

Zhao P, Sharma AC, Ren J

Title

Pathogenesis and therapy of autoimmunity-induced dilated cardiomyopathy.

Journal

Front Biosci 14:1708-15 (2009)

Reference

PMID:11716909

Authors

Franz WM, Muller OJ, Katus HA

Title

Cardiomyopathies: from genetics to the prospect of treatment.

Journal

Lancet 358:1627-37 (2001)

Reference

PMID:11805847

Authors

Towbin JA, Bowles NE

Title

The failing heart.

Journal

Nature 415:227-33 (2002)

Reference

PMID:19017683

Authors

Luk A, Ahn E, Soor GS, Butany J

Title

Dilated cardiomyopathy: a review.

Journal

J Clin Pathol 62:219-25 (2009)

Reference

PMID:19246813

Authors

Yoshikawa T, Baba A, Nagatomo Y

Title

Autoimmune mechanisms underlying dilated cardiomyopathy.

Journal

Circ J 73:602-7 (2009)

Reference

PMID:14522402

Authors

Mason JW

Title

Myocarditis and dilated cardiomyopathy: an inflammatory link.

Journal

Cardiovasc Res 60:5-10 (2003)

Reference

PMID:15146239

Authors

Jahns R, Boivin V, Hein L, Triebel S, Angermann CE, Ertl G, Lohse MJ

Title

Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy.

Journal

J Clin Invest 113:1419-29 (2004)

Reference

PMID:11524405

Authors

Liu PP, Mason JW

Title

Advances in the understanding of myocarditis.

Journal

Circulation 104:1076-82 (2001)

Reference

PMID:16817756

Authors

Tam PE

Title

Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.

Journal

Viral Immunol 19:133-46 (2006)

KO pathway

ko05414

All links

Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
   BioSystems (1)   
Disease (2)   
   KEGG DISEASE (2)   
Genome (1)   
   KEGG GENOME (1)   
Gene (91)   
   KEGG GENES (91)   
All databases (98)   

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