ArticleCirculation research2011
Hyperphosphorylation of mouse cardiac titin contributes to transverse aortic constriction-induced diastolic dysfunction.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Phenotype-specific muscle proteomic profiling in titinopathies.Acta neuropathologica communications · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Glycerol storage increases passive stiffness of muscle fibers through effects on titin extensibility.The Journal of general physiology · 2025Article
- Titin is a new factor regulating arterial stiffness through vascular smooth muscle cell tone in male rats.Physiological reports · 2025Article
- Congenital Titinopathies Linked to Mutations inInternational journal of molecular sciences · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Efficacy of a growth hormone-releasing hormone agonist in a murine model of cardiometabolic heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2023Article
- Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Investigation into the protective effects of hypaconitine and glycyrrhetinic acid against chronic heart failure of the rats.BMC complementary medicine and therapies · 2022Article
- The Cardiomyocyte in Heart Failure with Preserved Ejection Fraction-Victim of Its Environment?Cells · 2022Review
- The thromboxane receptor antagonistFrontiers in cardiovascular medicine · 2022Article
- Commensal gut microbiota-derived acetate and propionate enhance heart adaptation in response to cardiac pressure overload in mice.Theranostics · 2022Article
- Myofilament Phosphorylation in Stem Cell Treated Diastolic Heart Failure.Circulation research · 2021Article
- Increased Expression of N2BA Titin Corresponds to More Compliant Myofibrils in Athlete's Heart.International journal of molecular sciences · 2021Article
- Binge Alcohol Exposure in Adolescence Impairs Normal Heart Growth.Journal of the American Heart Association · 2020Article
- A new congenital multicore titinopathy associated with fast myosin heavy chain deficiency.Annals of clinical and translational neurology · 2020Article
- Mix and (mis-)match - The mechanosensing machinery in the changing environment of the developing, healthy adult and diseased heart.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Compliant Titin Isoform Content Is Reduced in Left Ventricles of Sedentary Versus Active Rats.Frontiers in physiology · 2020Article
- Posttranslational modifications of titin from cardiac muscle: how, where, and what for?The FEBS journal · 2019Review
- Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance.The Journal of general physiology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
rationaleMechanisms underlying diastolic dysfunction need to be better understood.
objectiveTo study the role of titin in diastolic dysfunction using a mouse model of experimental heart failure induced by transverse aortic constriction. METHODS AND
resultsEight weeks after transverse aortic constriction surgery, mice were divided into heart failure (HF) and congestive heart failure (CHF) groups. Mechanical studies on skinned left ventricle myocardium measured total and titin-based and extracellular matrix-based passive stiffness. Total passive stiffness was increased in both HF and CHF mice, and this was attributable to increases in both extracellular matrix-based and titin-based passive stiffness, with titin being dominant. Protein expression and titin exon microarray analysis revealed increased expression of the more compliant N2BA isoform at the expense of the stiff N2B isoform in HF and CHF mice. These changes are predicted to lower titin-based stiffness. Because the stiffness of titin is also sensitive to titin phosphorylation by protein kinase A and protein kinase C, back phosphorylation and Western blot assays with novel phospho-specific antibodies were performed. HF and CHF mice showed hyperphosphorylation of protein kinase A sites and the proline glutamate valine lysine (PEVK) S26 protein kinase C sites, but hypophosphorylation of the PEVK S170 protein kinase C site. Protein phosphatase I abolished differences in phosphorylation levels and normalized titin-based passive stiffness levels between control and HF myocardium.
conclusionTransverse aortic constriction-induced HF results in increased extracellular matrix-based and titin-based passive stiffness. Changes in titin splicing occur, which lower passive stiffness, but this effect is offset by hyperphosphorylation of residues in titin spring elements, particularly of PEVK S26. Thus, complex changes in titin occur that combined are a major factor in the increased passive myocardial stiffness in HF.
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Registered trials
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