ArticleCirculation2013
Shortening of the elastic tandem immunoglobulin segment of titin leads to diastolic dysfunction.
Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
59 citing papers in PubMed, 98 citations in OpenAlex.
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Titin's P-zone domains A164-167 are essential for thick filament structural arrangement.The Journal of general physiology · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Titin Cardiomyopathy, Emerging Evidence: More Than A Big Heart.Current cardiology reports · 2025Review
- Theoretical analysis of power-law stress relaxation and calcium-dependent passive mechanics in cardiac muscle.The Journal of physiology · 2025Article
- Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease.Nature biomedical engineering · 2025Article
- Differences in cardiac adaptation to exercise in male and female athletes assessed by noninvasive techniques: a state-of-the-art review.American journal of physiology. Heart and circulatory physiology · 2024Review
- Use of animal models to understand titin physiology and pathology.Journal of cellular and molecular medicine · 2022Review
- Right ventricular diastolic dysfunction and failure: a review.Heart failure reviews · 2022Review
- RBM20, a Therapeutic Target to Alleviate Myocardial StiffnessFrontiers in cardiovascular medicine · 2022Review
- Protein nanomechanics in biological context.Biophysical reviews · 2021Review
- Novel insights into sarcomere regulatory systems control of cardiac thin filament activation.The Journal of general physiology · 2021Article
- Mechanisms ofJournal of cardiovascular development and disease · 2021Review
- Transcriptional, Electrophysiological, and Metabolic Characterizations of hESC-Derived First and Second Heart Fields Demonstrate a Potential Role of TBX5 in Cardiomyocyte Maturation.Frontiers in cell and developmental biology · 2021Article
- Maintenance of sarcomeric integrity in adult muscle cells crucially depends on Z-disc anchored titin.Nature communications · 2020Article
- Binge Alcohol Exposure in Adolescence Impairs Normal Heart Growth.Journal of the American Heart Association · 2020Article
- Deleting Titin's C-Terminal PEVK Exons Increases Passive Stiffness, Alters Splicing, and Induces Cross-Sectional and Longitudinal Hypertrophy in Skeletal Muscle.Frontiers in physiology · 2020Article
- Single-Molecule Force Spectroscopy on the N2A Element of Titin: Effects of Phosphorylation and CARP.Frontiers in physiology · 2020Article
- Compliant Titin Isoform Content Is Reduced in Left Ventricles of Sedentary Versus Active Rats.Frontiers in physiology · 2020Article
- Stretching single titin molecules from failing human hearts reveals titin's role in blunting cardiac kinetic reserve.Cardiovascular research · 2020Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundDiastolic dysfunction is a poorly understood but clinically pervasive syndrome that is characterized by increased diastolic stiffness. Titin is the main determinant of cellular passive stiffness. However, the physiological role that the tandem immunoglobulin (Ig) segment of titin plays in stiffness generation and whether shortening this segment is sufficient to cause diastolic dysfunction need to be established. METHODS AND
resultsWe generated a mouse model in which 9 Ig-like domains (Ig3-Ig11) were deleted from the proximal tandem Ig segment of the spring region of titin (IG KO). Exon microarray analysis revealed no adaptations in titin splicing, whereas novel phospho-specific antibodies did not detect changes in titin phosphorylation. Passive myocyte stiffness was increased in the IG KO, and immunoelectron microscopy revealed increased extension of the remaining titin spring segments as the sole likely underlying mechanism. Diastolic stiffness was increased at the tissue and organ levels, with no consistent changes in extracellular matrix composition or extracellular matrix-based passive stiffness, supporting a titin-based mechanism for in vivo diastolic dysfunction. Additionally, IG KO mice have a reduced exercise tolerance, a phenotype often associated with diastolic dysfunction.
conclusionsIncreased titin-based passive stiffness is sufficient to cause diastolic dysfunction with exercise intolerance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.