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Review
. 2021 Oct 15;22(20):11154.
doi: 10.3390/ijms222011154.

Cardiomyocyte Dysfunction in Inherited Cardiomyopathies

Roua Hassoun  1   2 , Heidi Budde  1   2 , Andreas Mügge  1   2 , Nazha Hamdani  1   2
Affiliations
Review

Cardiomyocyte Dysfunction in Inherited Cardiomyopathies

Roua Hassoun et al. Int J Mol Sci. .

Abstract

Inherited cardiomyopathies form a heterogenous group of disorders that affect the structure and function of the heart. Defects in the genes encoding sarcomeric proteins are associated with various perturbations that induce contractile dysfunction and promote disease development. In this review we aimed to outline the functional consequences of the major inherited cardiomyopathies in terms of myocardial contraction and kinetics, and to highlight the structural and functional alterations in some sarcomeric variants that have been demonstrated to be involved in the pathogenesis of the inherited cardiomyopathies. A particular focus was made on mutation-induced alterations in cardiomyocyte mechanics. Since no disease-specific treatments for familial cardiomyopathies exist, several novel agents have been developed to modulate sarcomere contractility. Understanding the molecular basis of the disease opens new avenues for the development of new therapies. Furthermore, the earlier the awareness of the genetic defect, the better the clinical prognostication would be for patients and the better the prevention of development of the disease.

Keywords: cardiomyocyte mechanics; inherited cardiomyopathies; mutations; sarcomeric proteins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme demonstrating the morphological features of HCM, DCM, and RCM.
Figure 2
Figure 2
Schematic representation of the cardiomyocyte demonstrating sarcomeric genes with subcellular localization of the encoded protein. TNNT2 = cardiac troponin T2; TNNI3 = cardiac troponin I; TNNC1 = cardiac troponin C; TPM1 = α-tropomyosin; TTN = titin; ACTC1 = α-cardiac actin; MYH7 = β-myosin heavy chain; MYBPC3 = cardiac myosin binding protein C.
Figure 3
Figure 3
(A). Effects of cTnI phosphorylation on myocyte Ca2+ sensitivity. (B). Effects of titin phosphorylation on myocyte passive stiffness.
See this image and copyright information in PMC

References

    1. Semsarian C., Ingles J., Maron M.S., Maron B.J. New Perspectives on the Prevalence of Hypertrophic Cardiomyopathy. J. Am. Coll. Cardiol. 2015;65:1249–1254. doi: 10.1016/j.jacc.2015.01.019. - DOI - PubMed
    1. Marian A.J., Braunwald E. Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circ. Res. 2017;121:749–770. doi: 10.1161/CIRCRESAHA.117.311059. - DOI - PMC - PubMed
    1. Hershberger R.E., Hedges D.J., Morales A. Dilated Cardiomyopathy: The Complexity of a Diverse Genetic Architecture. Nat. Rev. Cardiol. 2013;10:531–547. doi: 10.1038/nrcardio.2013.105. - DOI - PubMed
    1. Elliott P., Andersson B., Arbustini E., Bilinska Z., Cecchi F., Charron P., Dubourg O., Kühl U., Maisch B., McKenna W.J., et al. Classification of the Cardiomyopathies: A Position Statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur. Heart J. 2008;29:270–276. doi: 10.1093/eurheartj/ehm342. - DOI - PubMed
    1. Fatkin D., Graham R.M. Molecular Mechanisms of Inherited Cardiomyopathies. Physiol. Rev. 2002;82:945–980. doi: 10.1152/physrev.00012.2002. - DOI - PubMed