Ramone Eldemire1, Charles A Tharp1, Matthew R G Taylor1,2, Orfeo Sbaizero1,3, Luisa Mestroni4,5. 1. University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. 2. Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. 3. Department of Engineering and Architecture, University of Trieste, 34127, Trieste, Italy. 4. University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. LUISA.MESTRONI@CUANSCHUTZ.EDU. 5. 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@CUANSCHUTZ.EDU.
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. 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.
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. 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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