Molecular Etiology of Idiopathic Cardiomyopathy

Overview

Journal Acta Myol

Date 2008 Jul 24

PMID 18646564

Citations 6

Authors

T Arimura

T Hayashi

A Kimura

Affiliations

Soon will be listed here.

Abstract

Idiopathic cardiomyopathy (ICM) is a primary cardiac disorder associated with abnormalities of ventricular wall thickness, size of ventricular cavity, contraction, relaxation, conduction and rhythm. Over the past two decades, molecular genetic analyses have revealed that mutations in the various genes cause ICM and such information concerning the genetic basis of ICM enables us to speculate the pathogenesis of this heterogeous cardiac disease. This review focuses on the molecular pathogenesis, i.e., genetic abnormalities and functional alterations due to the mutations especially in sarcomere/cytoskeletal components, in three characteristic features of ICM, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM). Understanding the functional abnormalities of the sarcomere/cytoskeletal components, in ICM, has unraveled the function of these components not only as a contractile unit but also as a pivot for transduction of biochemical signals.

Citing Articles

Exploring in vivo and in vitro models for heart failure with biomarker insights: a review.

Prajapati A, Shah G Egypt Heart J. 2024; 76(1):141.

PMID: 39432214 PMC: 11493927. DOI: 10.1186/s43044-024-00568-1.

Phenotypic Disease Network-Based Multimorbidity Analysis in Idiopathic Cardiomyopathy Patients with Hospital Discharge Records.

Wang L, Jin Y, Zhou J, Pang C, Wang Y, Zhang S J Clin Med. 2022; 11(23).

PMID: 36498544 PMC: 9736397. DOI: 10.3390/jcm11236965.

Pigs with δ-sarcoglycan deficiency exhibit traits of genetic cardiomyopathy.

Matsunari H, Honda M, Watanabe M, Fukushima S, Suzuki K, Miyagawa S Lab Invest. 2020; 100(6):887-899.

PMID: 32060408 PMC: 7280178. DOI: 10.1038/s41374-020-0406-7.

Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy.

Colak D, Alaiya A, Kaya N, Muiya N, AlHarazi O, Shinwari Z PLoS One. 2016; 11(10):e0162669.

PMID: 27711126 PMC: 5053516. DOI: 10.1371/journal.pone.0162669.

Titin mutations: the fall of Goliath.

Neiva-Sousa M, Almeida-Coelho J, Falcao-Pires I, Leite-Moreira A Heart Fail Rev. 2015; 20(5):579-88.

PMID: 26024954 DOI: 10.1007/s10741-015-9495-6.

References

Arimura T, Matsumoto Y, Okazaki O, Hayashi T, Takahashi M, Inagaki N . Structural analysis of obscurin gene in hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2007; 362(2):281-7. DOI: 10.1016/j.bbrc.2007.07.183. View

Mohapatra B, Jimenez S, Lin J, Bowles K, Coveler K, Marx J . Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. Mol Genet Metab. 2003; 80(1-2):207-15. DOI: 10.1016/s1096-7192(03)00142-2. View

Lange S, Auerbach D, McLoughlin P, Perriard E, Schafer B, Perriard J . Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2. J Cell Sci. 2002; 115(Pt 24):4925-36. DOI: 10.1242/jcs.00181. View

Inagaki N, Hayashi T, Arimura T, Koga Y, Takahashi M, Shibata H . Alpha B-crystallin mutation in dilated cardiomyopathy. Biochem Biophys Res Commun. 2006; 342(2):379-86. DOI: 10.1016/j.bbrc.2006.01.154. View

Bos J, Ommen S, Ackerman M . Genetics of hypertrophic cardiomyopathy: one, two, or more diseases?. Curr Opin Cardiol. 2007; 22(3):193-9. DOI: 10.1097/HCO.0b013e3280e1cc7f. View

Arbustini E, Pasotti M, Pilotto A, Pellegrini C, Grasso M, Previtali S . Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail. 2005; 8(5):477-83. DOI: 10.1016/j.ejheart.2005.11.003. View

Chen J, Chien K . Complexity in simplicity: monogenic disorders and complex cardiomyopathies. J Clin Invest. 1999; 103(11):1483-5. PMC: 408378. DOI: 10.1172/JCI7297. View

Morimoto S, Harada K, Minakami R, Ohta M, Sasaguri T, Ohtsuki I . Ca(2+)-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy. Proc Natl Acad Sci U S A. 2002; 99(2):913-8. PMC: 117405. DOI: 10.1073/pnas.022628899. View

Knoll R, Hoshijima M, Hoffman H, Person V, Lorenzen-Schmidt I, Bang M . The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell. 2003; 111(7):943-55. DOI: 10.1016/s0092-8674(02)01226-6. View

10.

Kimura A, Hayashi T, Takahashi M, Arimura T . Molecular etiology of idiopathic cardiomyopathy in Asian populations. J Cardiol. 2001; 37 Suppl 1:139-46. View

11.

Schonberger J, Wang L, Shin J, Kim S, Depreux F, Zhu H . Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet. 2005; 37(4):418-22. DOI: 10.1038/ng1527. View

12.

Richardson P, McKenna W, Bristow M, Maisch B, MAUTNER B, OConnell J . Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. 1996; 93(5):841-2. DOI: 10.1161/01.cir.93.5.841. View

13.

Chien K, Olson E . Converging pathways and principles in heart development and disease: CV@CSH. Cell. 2002; 110(2):153-62. DOI: 10.1016/s0092-8674(02)00834-6. View

14.

Arimura T, Hayashi T, Terada H, Lee S, Zhou Q, Takahashi M . A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C. J Biol Chem. 2003; 279(8):6746-52. DOI: 10.1074/jbc.M311849200. View

15.

Maron B, Towbin J, Thiene G, Antzelevitch C, Corrado D, Arnett D . Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and.... Circulation. 2006; 113(14):1807-16. DOI: 10.1161/CIRCULATIONAHA.106.174287. View

16.

Arimura T, Hayashi T, Matsumoto Y, Shibata H, Hiroi S, Nakamura T . Structural analysis of four and half LIM protein-2 in dilated cardiomyopathy. Biochem Biophys Res Commun. 2007; 357(1):162-7. DOI: 10.1016/j.bbrc.2007.03.128. View

17.

Li D, Tapscoft T, Gonzalez O, Burch P, Quinones M, Zoghbi W . Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation. 1999; 100(5):461-4. DOI: 10.1161/01.cir.100.5.461. View

18.

Towbin J . The role of cytoskeletal proteins in cardiomyopathies. Curr Opin Cell Biol. 1998; 10(1):131-9. DOI: 10.1016/s0955-0674(98)80096-3. View

19.

Matsumoto Y, Hayashi T, Inagaki N, Takahashi M, Hiroi S, Nakamura T . Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy. J Muscle Res Cell Motil. 2006; 26(6-8):367-74. DOI: 10.1007/s10974-005-9018-5. View

20.

Michels V, Moll P, Miller F, Tajik A, Chu J, Driscoll D . The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med. 1992; 326(2):77-82. DOI: 10.1056/NEJM199201093260201. View