April 7, 2007Cardiovascular Research
Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction
Design
Review
Authors
Discussion
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Implication
Hypothesis-generating for titin-targeted therapies in heart failure; leaves clinical translation open pending targeted trials.
Key Points
- To review the mechanosensory functions of titin and titin-associated protein complexes in cardiomyocyte stress-sensing, passive stiffness regulation, and cardiac disease.
- Synthesized molecular and mechanical evidence regarding titin's structural domains across the sarcomere, specifically the Z-disk, elastic I-band, and M-band.
- Evaluated the functional interactions of titin with over 20 binding partners and analyzed disease-causing mutations associated with cardiac remodeling and myopathies.
- Identified the elastic I-band section of titin as the primary molecular determinant of diastolic distensibility and passive myocardial stiffness.
- Characterized putative mechanosensing complexes localized at titin's NH2- and COOH-termini that alter contractile function and gene expression under mechanical stress.
- Demonstrated that disruption of titin-based stretch-sensor complexes drives pathological cardiac remodeling, mechanical dysfunction, and heart failure.
Cite This Study
Wolfgang A. Linke (2007) studied this question.