Genetic causes of human heart failure
Hiroyuki Morita, … , Jonathan Seidman, Christine E. Seidman
Hiroyuki Morita, … , Jonathan Seidman, Christine E. Seidman
Published March 1, 2005
Citation Information: J Clin Invest. 2005;115(3):518-526. https://doi.org/10.1172/JCI24351.
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Genetic causes of human heart failure

Abstract

Factors that render patients with cardiovascular disease at high risk for heart failure remain incompletely defined. Recent insights into molecular genetic causes of myocardial diseases have highlighted the importance of single-gene defects in the pathogenesis of heart failure. Through analyses of the mechanisms by which a mutation selectively perturbs one component of cardiac physiology and triggers cell and molecular responses, studies of human gene mutations provide a window into the complex processes of cardiac remodeling and heart failure. Knowledge gleaned from these studies shows promise for defining novel therapeutic targets for genetic and acquired causes of heart failure.

Authors

Hiroyuki Morita, Jonathan Seidman, Christine E. Seidman

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Human mutations affecting contractile and Z-disc proteins. The schematic...
Human mutations affecting contractile and Z-disc proteins. The schematic depicts one sarcomere, the fundamental unit of contraction encompassing the protein segment between flanking Z discs. Sarcomere thin filament proteins are composed of actin and troponins C, T, and I. Sarcomere thick filament proteins include myosin heavy chain, myosin essential and regulatory light chains, myosin-binding protein-C and titin. The sarcomere is anchored through titin and actin interactions with Z disc proteins α-actinin, calsarcin-1, MLP, telethonin (T-cap), and ZASP. Human mutations (orange text) in contractile proteins and Z-disc proteins can cause HCM or DCM.