ArticleThe Journal of clinical investigation1999
Identification of a contractile deficit in adult cardiac myocytes expressing hypertrophic cardiomyopathy-associated mutant troponin T proteins.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 109 citations in OpenAlex.
- A bioinformatic survey of RNA isoform diversity and expression across 9 GTEx tissues using long-read sequencing data.BMC genomics · 2025Article
- Genotype-Phenotype Associations with Restrictive Cardiomyopathy Induced by Pathogenic Genetic Mutations.Reviews in cardiovascular medicine · 2022Review
- Role of global longitudinal strain in discriminating variant forms of left ventricular hypertrophy and predicting mortality.Anatolian journal of cardiology · 2021Article
- Mechanical dysfunction of the sarcomere induced by a pathogenic mutation in troponin T drives cellular adaptation.The Journal of general physiology · 2021Article
- Complexity in genetic cardiomyopathies and new approaches for mechanism-based precision medicine.The Journal of general physiology · 2021Article
- Mechanisms of Arrhythmogenicity of Hypertrophic Cardiomyopathy-Associated Troponin T (Frontiers in cell and developmental biology · 2021Article
- INDUCED PLURIPOTENT STEM CELLS FOR MODELLING ENERGETIC ALTERATIONS IN HYPERTROPHIC CARDIOMYOPATHY.Conditioning medicine · 2019Article
- Assessment of left ventricular systolic and diastolic abnormalities in patients with hypertrophic cardiomyopathy using real-time three-dimensional echocardiography and two-dimensional speckle tracking imaging.Cardiovascular ultrasound · 2018Article
- Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.Journal of molecular and cellular cardiology · 2018Article
- Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility.Archives of biochemistry and biophysics · 2016Review
- Gene transfer into cardiac myocytes.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.Anatomical record (Hoboken, N.J. : 2007) · 2014Review
- Reduction of left ventricular longitudinal global and segmental systolic functions in patients with hypertrophic cardiomyopathy: Study of two-dimensional tissue motion annular displacement.Experimental and therapeutic medicine · 2014Article
- Analysis of the molecular pathogenesis of cardiomyopathy-causing cTnT mutants I79N, ΔE96, and ΔK210.Biophysical journal · 2013Article
- Hypertrophic cardiomyopathy: from genetics to treatment.European journal of clinical investigation · 2010Review
- Cardiac troponin mutations and restrictive cardiomyopathy.Journal of biomedicine & biotechnology · 2010Review
- Experimental therapies in hypertrophic cardiomyopathy.Journal of cardiovascular translational research · 2009Review
- Threonine-5 at the N-terminus can modulate sarcolipin function in cardiac myocytes.Journal of molecular and cellular cardiology · 2009Article
- Cardiac troponin T mutation in familial cardiomyopathy with variable remodeling and restrictive physiology.Clinical genetics · 2008Article
- A novel mutant cardiac troponin C disrupts molecular motions critical for calcium binding affinity and cardiomyocyte contractility.Biophysical journal · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The direct effects of expressing hypertrophic cardiomyopathy-associated (HCM-associated) mutant troponin T (TnT) proteins on the force generation of single adult cardiac myocytes have not been established. Replication-defective recombinant adenovirus vectors were generated for gene transfer of HCM-associated I79N and R92Q mutant cardiac TnT cDNAs into fully differentiated adult cardiac myocytes in primary culture. We tested the hypothesis that the mutant TnT proteins would be expressed and incorporated into the cardiac sarcomere and would behave as dominant-negative proteins to directly alter calcium-activated force generation at the level of the single cardiac myocyte. Interestingly, under identical experimental conditions, the ectopic expression of the mutant TnTs was significantly less ( approximately 8% of total) than that obtained with expression of wild-type TnT ( approximately 35%) in the myocytes. Confocal imaging of immunolabeled TnT showed a regular periodic pattern of localization of ectopic mutant TnT that was not different than that in normal controls, suggesting that mutant TnT incorporation had no deleterious effects on sarcomeric architecture. Direct measurements of isometric force production in single cardiac myocytes demonstrated marked desensitization of submaximal calcium-activated tension, with unchanged maximum tension generation in mutant TnT-expressing myocytes compared with control myocytes. Collectively, these results demonstrate an impaired expression of the mutant protein and a disabling of cardiac contraction in the submaximal range of myoplasmic calcium concentrations. Our functional results suggest that development of new pharmacological, chemical, or genetic approaches to sensitize the thin-filament regulatory protein system could ameliorate force deficits associated with expression of I79N and R92Q in adult cardiac myocytes.
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