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The Sarcomeric Spring Protein Titin: Biophysical Properties, Molecular Mechanisms, and Genetic Mutations Associated with Heart Failure and Cardiomyopathy

  • Myocardial Disease (A Abbate and G Sinagra, Section Editors)
  • Published:
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Abstract

Purpose of Review

The giant protein titin forms the “elastic” filament of the sarcomere, essential for the mechanical compliance of the heart muscle. Titin serves a biological spring, and therefore structural modifications of titin affect function of the myocardium and are associated with heart failure and cardiomyopathy.

Recent Findings

In this review, we discuss the current understanding of titin’s biophysical properties and how modifications contribute to cardiac function and heart failure. In addition, we review the most recent data on the clinical impact and phenotype heterogeneity of TTN truncating variants, including diseases involving striated muscles, and prospects for future therapies.

Summary

Because of the giant structure of the titin protein and the complexity of its function, titin’s role in health and disease is not yet completely understood. Future research efforts need to focus on novel therapeutic approaches able to modulate titin transcriptional and post-translational modification.

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Funding

Supported by the NIH R01HL69071, HL116906, HL147064, NCATS Colorado CTSA/UL1 TR002535 and UL1 TR001082 (LM), NIH 1K23HI067915, NIH 2UM1HG006542 and R01HL109209 (MRGT), NHLBI T32HL007822 (CT), MIUR PRIN - 20173ZW (OS) and in part by a Trans-Atlantic Network of Excellence grant from the Fondation Leducq 14-CVD03 (LM, MRGT, OS).

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Authors and Affiliations

  1. University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA

    Ramone Eldemire, Charles A. Tharp, Matthew R.G. Taylor, Orfeo Sbaizero & Luisa Mestroni

  2. Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA

    Matthew R.G. Taylor

  3. Department of Engineering and Architecture, University of Trieste, 34127, Trieste, Italy

    Orfeo Sbaizero

  4. Molecular Genetics, Cardiovascular Institute, University of Colorado Anschutz Medical Campus, 12700 E 19th Ave # F442, RC2, Room 8021, Aurora, CO, 80045-2507, USA

    Luisa Mestroni

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  1. Ramone Eldemire
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Correspondence to Luisa Mestroni.

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Eldemire, R., Tharp, C.A., Taylor, M.R. et al. The Sarcomeric Spring Protein Titin: Biophysical Properties, Molecular Mechanisms, and Genetic Mutations Associated with Heart Failure and Cardiomyopathy. Curr Cardiol Rep 23, 121 (2021). https://doi.org/10.1007/s11886-021-01550-y

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