ArticleJournal of molecular and cellular cardiology2022
Myofilament glycation in diabetes reduces contractility by inhibiting tropomyosin movement, is rescued by cMyBPC domains.
Article in Journal of molecular and cellular cardiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- The AGE-RAGE-DIAPH1 Axis in Type 2 Diabetes and Metabolic Dysfunction: From Carbonyl Stress to Diabetic Myocardial and Neuronal Injury.International journal of molecular sciences · 2026Review
- Changes in cardiac myosin acetylation disrupt the super-relaxed state in genotype-negative hypertrophic cardiomyopathy with type 2 diabetes.Cardiovascular diabetology · 2026Article
- Destabilization of cardiac myosin acetylation and sequestration with type 2 diabetes mellitus.Cardiovascular diabetology · 2026Article
- Aerobic exercise training attenuates cardiac inflammation and fibrosis in mice with type 2 diabetes and inhibits the advanced glycation end products pathway.Diabetology & metabolic syndrome · 2026Article
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
- Potential of Natural Products in Hangeshashinto Water Extract on the Direct Suppression of Stomatitis Induced by Intra-/Extracellular Advanced Glycation End-Products.International journal of molecular sciences · 2025Review
- Biaxial length-tension relationship in single cardiac myocytes.Biophysical journal · 2025Article
- Dysregulated skeletal muscle myosin super-relaxation and energetics in male participants with type 2 diabetes mellitus.Diabetologia · 2025Article
- Cystatin-c / total cholesterol ratio as a predictor of probable sarcopenia in geriatric population from 12 European countries.Aging clinical and experimental research · 2025Article
- Slot Blot- and Electrospray Ionization-Mass Spectrometry/Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry-Based Novel Analysis Methods for the Identification and Quantification of Advanced Glycation End-Products in the Urine.International journal of molecular sciences · 2024Article
- Generation and Accumulation of Various Advanced Glycation End-Products in Cardiomyocytes May Induce Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Protein carbonylation causes sarcoplasmic reticulum CaPflugers Archiv : European journal of physiology · 2024Article
- Proteomics of the heart.Physiological reviews · 2024Review
- Article
- Assessing Cardiac Contractility From Single Molecules to Whole Hearts.JACC. Basic to translational science · 2024Review
- Protein carbonylation causes sarcoplasmic reticulum Ca2+ overload by increasing intracellular Na+ level in ventricular myocytes.Research square · 2024Article
- Glycation in the cardiomyocyte.Vitamins and hormones · 2024Review
- Single-molecule mechanics and kinetics of cardiac myosin interacting with regulated thin filaments.Biophysical journal · 2023Article
- Functional assays reveal the pathogenic mechanism of a de novo tropomyosin variant identified in patient with dilated cardiomyopathy.Journal of molecular and cellular cardiology · 2023Article
- Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Diabetes doubles the risk of developing heart failure (HF). As the prevalence of diabetes grows, so will HF unless the mechanisms connecting these diseases can be identified. Methylglyoxal (MG) is a glycolysis by-product that forms irreversible modifications on lysine and arginine, called glycation. We previously found that myofilament MG glycation causes sarcomere contractile dysfunction and is increased in patients with diabetes and HF. The aim of this study was to discover the molecular mechanisms by which MG glycation of myofilament proteins cause sarcomere dysfunction and to identify therapeutic avenues to compensate. In humans with type 2 diabetes without HF, we found increased glycation of sarcomeric actin compared to non-diabetics and it correlated with decreased calcium sensitivity. Depressed calcium sensitivity is pathogenic for HF, therefore myofilament glycation represents a promising therapeutic target to inhibit the development of HF in diabetics. To identify possible therapeutic targets, we further defined the molecular actions of myofilament glycation. Skinned myocytes exposed to 100 μM MG exhibited decreased calcium sensitivity, maximal calcium-activated force, and crossbridge kinetics. Replicating MG's functional affects using a computer simulation of sarcomere function predicted simultaneous decreases in tropomyosin's blocked-to-closed rate transition and crossbridge duty cycle were consistent with all experimental findings. Stopped-flow experiments and ATPase activity confirmed MG decreased the blocked-to-closed transition rate. Currently, no therapeutics target tropomyosin, so as proof-of-principal, we used a n-terminal peptide of myosin-binding protein C, previously shown to alter tropomyosin's position on actin. C0C2 completely rescued MG-induced calcium desensitization, suggesting a possible treatment for diabetic HF.
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