ArticleJournal of molecular and cellular cardiology2015
Increased myocardial stiffness due to cardiac titin isoform switching in a mouse model of volume overload limits eccentric remodeling.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- A unified finite element framework for cardiac growth and remodeling in mitral regurgitation incorporating fiber reorientation and baroreflex.Acta biomaterialia · 2026Article
- Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF).Cardiovascular research · 2025Article
- Adaptive and Pathological Changes of the Cardiac Muscle in a Mouse Model of Renocardiac Syndrome: The Role of Nestin-Positive Cells.International journal of molecular sciences · 2025Article
- Novel Drug Targets in Diastolic Heart Disease.International journal of molecular sciences · 2025Review
- Titin's cardiac-specific N2B element is critical to mechanotransduction during volume overload of the heart.Journal of molecular and cellular cardiology · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy.Journal of molecular and cellular cardiology · 2023Article
- GSK-3β Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation.Circulation research · 2022Article
- Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation.Science advances · 2022Article
- RBM20, a Therapeutic Target to Alleviate Myocardial StiffnessFrontiers in cardiovascular medicine · 2022Review
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- Right versus left ventricular remodeling in heart failure due to chronic volume overload.Scientific reports · 2021Article
- Paired Pressure-Volume Loop Analysis and Biaxial Mechanical Testing Characterize Differences in Left Ventricular Tissue Stiffness of Volume Overload and Angiotensin-Induced Pressure Overload Hearts.Journal of biomechanical engineering · 2021Article
- Functional analysis of a gene-edited mouse model to gain insights into the disease mechanisms of a titin missense variant.Basic research in cardiology · 2021Article
- Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis.Frontiers in physiology · 2021Article
- Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation.Frontiers in cardiovascular medicine · 2021Article
- A missense mutation in the RSRSP stretch of Rbm20 causes dilated cardiomyopathy and atrial fibrillation in mice.Scientific reports · 2020Article
- New Insights in RBM20 Cardiomyopathy.Current heart failure reports · 2020Review
- Heart Plasticity in Response to Pressure- and Volume-Overload: A Review of Findings in Compensated and Decompensated Phenotypes.Frontiers in physiology · 2020Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We investigated the cellular and molecular mechanisms of diastolic dysfunction in pure volume overload induced by aortocaval fistula (ACF) surgery in the mouse. Four weeks of volume overload resulted in significant biventricular hypertrophy; protein expression analysis in left ventricular (LV) tissue showed a marked decrease in titin's N2BA/N2B ratio with no change in phosphorylation of titin's spring region. Titin-based passive tensions were significantly increased; a result of the decreased N2BA/N2B ratio. Conscious echocardiography in ACF mice revealed eccentric remodeling and pressure volume analysis revealed systolic dysfunction: reductions in ejection fraction (EF), +dP/dt, and the slope of the end-systolic pressure volume relationships (ESPVR). ACF mice also had diastolic dysfunction: increased LV end-diastolic pressure and reduced relaxation rates. Additionally, a decrease in the slope of the end diastolic pressure volume relationship (EDPVR) was found. However, correcting for altered geometry of the LV normalized the change in EDPVR and revealed, in line with our skinned muscle data, increased myocardial stiffness in vivo. ACF mice also had increased expression of the signaling proteins FHL-1, FHL-2, and CARP that bind to titin's spring region suggesting that titin stiffening is important to the volume overload phenotype. To test this we investigated the effect of volume overload in the RBM20 heterozygous (HET) mouse model, which exhibits reduced titin stiffness. It was found that LV hypertrophy was attenuated and that LV eccentricity was exacerbated. We propose that pure volume overload induces an increase in titin stiffness that is beneficial and limits eccentric remodeling.
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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.