ArticleProceedings of the National Academy of Sciences of the United States of America2020
Regulation of titin-based cardiac stiffness by unfolded domain oxidation (UnDOx).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.Frontiers in cardiovascular medicine · 2022Pooled it
- A quantitative redox proteome of the human muscle response to exercise.bioRxiv : the preprint server for biology · 2026Article
- Integration of multiple perspectives to understand the left ventricular pressure-volume relationship.Communications medicine · 2026Review
- PITX2C deficiency promotes arrhythmogenic remodelling via oxidative stress in atrial myocytes.Journal of molecular and cellular cardiology plus · 2026Article
- Inflammation, metabolism, and aging in heart failure with preserved ejection fraction: Mechanisms and treatment perspectives.Journal of translational internal medicine · 2026Article
- Ferroportin inhibition attenuates pulmonary hypertension in hypoxic sickle cell disease mice.Blood advances · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Diabetes and cancer: therapeutic implications.Cardio-oncology (London, England) · 2026Review
- Titin modulation and left ventricular remodelling in chronic primary mitral regurgitation.Frontiers in cardiovascular medicine · 2026Article
- Skeletal muscle knockout of NAD(P)H oxidase 2 delays the development of isotonic diaphragm fatigue in mice.Free radical biology & medicine · 2025Article
- Diabetes mellitus aggravates myocardial inflammation and oxidative stress in aortic stenosis: a mechanistic link to HFpEF features.Cardiovascular diabetology · 2025Article
- Decreased antioxidant-related superoxide dismutase 1 expression in peripheral immune cells indicates early ethanol exposure.Scientific reports · 2024Article
- Structural domain in the Titin N2B-us region binds to FHL2 in a force-activation dependent manner.Nature communications · 2024Article
- Emerging Concepts of Mechanisms Controlling Cardiac Tension: Focus on Familial Dilated Cardiomyopathy (DCM) and Sarcomere-Directed Therapies.Biomedicines · 2024Review
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Titin governs myocardial passive stiffness with major support from microtubules and actin and the extracellular matrix.Nature cardiovascular research · 2023Article
- Chemistry and biology of enzymes in protein glutathionylation.Current opinion in chemical biology · 2023Review
- Pore-like diffusion barriers in murine cardiac myocytes.bioRxiv : the preprint server for biology · 2023Article
- Emerging chemistry and biology in protein glutathionylation.Current opinion in chemical biology · 2022Review
- Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The relationship between oxidative stress and cardiac stiffness is thought to involve modifications to the giant muscle protein titin, which in turn can determine the progression of heart disease. In vitro studies have shown that S-glutathionylation and disulfide bonding of titin fragments could alter the elastic properties of titin; however, whether and where titin becomes oxidized in vivo is less certain. Here we demonstrate, using multiple models of oxidative stress in conjunction with mechanical loading, that immunoglobulin domains preferentially from the distal titin spring region become oxidized in vivo through the mechanism of unfolded domain oxidation (UnDOx). Via oxidation type-specific modification of titin, UnDOx modulates human cardiomyocyte passive force bidirectionally. UnDOx also enhances titin phosphorylation and, importantly, promotes nonconstitutive folding and aggregation of unfolded domains. We propose a mechanism whereby UnDOx enables the controlled homotypic interactions within the distal titin spring to stabilize this segment and regulate myocardial passive stiffness.
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