ArticleNature medicine2018
Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.
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Who cites it
182 citing papers in PubMed, 274 citations in OpenAlex.
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Human adult and pediatric multimodal transcriptomic atlas of progression from pressure-loaded to failing right ventricle.Nature cardiovascular research · 2026Article
- Cardiac proteomic and phosphoproteomic profiling defines clinically relevant molecular subgroups in human heart failure.Nature cardiovascular research · 2026Article
- Microtubule posttranslational modifications provide unique recognition patterns for associated proteins.The EMBO journal · 2026Article
- Vasohibin 1 acts as a key regulator of arrhythmogenesis in pressure-overload-induced cardiac hypertrophy.Acta pharmacologica Sinica · 2026Article
- From biomechanical mechanisms to clinical reasoning: Deciphering mechanobiological drivers of aortic valve calcification for precision therapy.Mechanobiology in medicine · 2026Review
- Towards a systems-level view of the microtubule cytoskeleton and its functions in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- TUBA4A: The Tale of an Unconventional Tubulin.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Condensation of MATCAP promotes CENP-E-dependent chromosome congression in mitosis.Nature communications · 2026Article
- Targeting Arrhythmogenic Late Sodium Current by FHF1Circulation research · 2026Article
- Decreasing Microtubule Detyrosination Improves Cardiac Mechanics and Sodium Channel Function in Arrhythmogenic Cardiomyopathy.Circulation. Arrhythmia and electrophysiology · 2026Article
- SORBS2 regulates diastolic function through cytoskeletal networks and calcium handling.Communications biology · 2026Article
- MATCAP1 preferentially binds an expanded tubulin conformation to generate detyrosinated and ΔC2 α-tubulin.The EMBO journal · 2026Article
- Right Heart Diastology, Where Are We Now?Circulation research · 2026Review
- Spastin-mediated severing of glutamylated microtubules controls cardiomyocyte coupling.Nature cardiovascular research · 2026Article
- The roles of the microtubule cytoskeletal network in cardiac mechanobiology.Journal of cell science · 2026Review
- Sarcomeric remodelling in human heart failure unraveled by single molecule long read sequencing.EMBO molecular medicine · 2026Article
- CPT1a Expression Is a Critical Cardioprotective Response to Pathological Stress That Enables Rescue by Gene Transfer.Circulation research · 2026Article
- Peptide-based covalent inhibitor of tubulin detyrosination promotes mesenchymal-to-epithelial transition in lung cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tubulin Post-Translational Modifications in Cardiovascular Diseases: Emerging Mechanisms and Therapeutic Modulation by Traditional Chinese Medicine.Drug design, development and therapy · 2026Review
122 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Detyrosinated microtubules provide mechanical resistance that can impede the motion of contracting cardiomyocytes. However, the functional effects of microtubule detyrosination in heart failure or in human hearts have not previously been studied. Here, we utilize mass spectrometry and single-myocyte mechanical assays to characterize changes to the cardiomyocyte cytoskeleton and their functional consequences in human heart failure. Proteomic analysis of left ventricle tissue reveals a consistent upregulation and stabilization of intermediate filaments and microtubules in failing human hearts. As revealed by super-resolution imaging, failing cardiomyocytes are characterized by a dense, heavily detyrosinated microtubule network, which is associated with increased myocyte stiffness and impaired contractility. Pharmacological suppression of detyrosinated microtubules lowers the viscoelasticity of failing myocytes and restores 40-50% of lost contractile function; reduction of microtubule detyrosination using a genetic approach also softens cardiomyocytes and improves contractile kinetics. Together, these data demonstrate that a modified cytoskeletal network impedes contractile function in cardiomyocytes from failing human hearts and that targeting detyrosinated microtubules could represent a new inotropic strategy for improving cardiac function.
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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.