ArticleCardiovascular research2008
Single histidine-substituted cardiac troponin I confers protection from age-related systolic and diastolic dysfunction.
Article in Cardiovascular research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Troponin T1 in tumorigenesis and immune modulation: Insights into multiple cancers and kidney renal clear cell carcinoma.Journal of cellular and molecular medicine · 2024Article
- Enhanced dimethylarginine degradation improves coronary flow reserve and exercise tolerance in Duchenne muscular dystrophy carrier mice.American journal of physiology. Heart and circulatory physiology · 2020Article
- Cytoplasmic nucleic acid-based XNAs directly enhance live cardiac cell function by a CaJournal of molecular and cellular cardiology · 2019Article
- TnI Structural Interface with the N-Terminal Lobe of TnC as a Determinant of Cardiac Contractility.Biophysical journal · 2018Article
- Measuring Pressure Volume Loops in the Mouse.Journal of visualized experiments : JoVE · 2016Article
- Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.Anatomical record (Hoboken, N.J. : 2007) · 2014Review
- Molecular determinants of cardiac myocyte performance as conferred by isoform-specific TnI residues.Biophysical journal · 2014Article
- Diastolic dysfunction and thin filament dysregulation resulting from excitation-contraction uncoupling in a mouse model of restrictive cardiomyopathy.Journal of molecular and cellular cardiology · 2012Article
- pH-responsive titratable inotropic performance of histidine-modified cardiac troponin I.Biophysical journal · 2012Article
- Loss of H3K4 methylation destabilizes gene expression patterns and physiological functions in adult murine cardiomyocytes.The Journal of clinical investigation · 2011Article
- Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies.American journal of physiology. Heart and circulatory physiology · 2011Article
- Pathogenic peptide deviations support a model of adaptive evolution of chordate cardiac performance by troponin mutations.Physiological genomics · 2010Article
- Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
- Molecular cardiology in translation: gene, cell and chemical-based experimental therapeutics for the failing heart.Journal of cardiovascular translational research · 2008Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
aimsContractile dysfunction associated with myocardial ischaemia is a significant cause of morbidity and mortality in the elderly. Strategies to protect the aged heart from ischaemia-mediated pump failure are needed. We hypothesized that troponin I-mediated augmentation of myofilament calcium sensitivity would protect cardiac function in aged mice. METHODS AND
resultsTo address this, we investigated transgenic (Tg) mice expressing a histidine-substituted form of adult cardiac troponin I (cTnI A164H), which increases myofilament calcium sensitivity in a pH-dependent manner. Serial echocardiography revealed that Tg hearts showed significantly improved systolic function at 4 months, which was sustained for 2 years based on ejection fraction and velocity of circumferential fibre shortening. Age-related diastolic dysfunction was also attenuated in Tg mice as assessed by Doppler measurements of the mitral valve inflow and lateral annulus Doppler tissue imaging. During acute hypoxia, cardiac contractility significantly improved in aged Tg mice made evident by increased stroke volume, end systolic pressure, and +dP/dt compared with non-transgenic mice.
conclusionThis study shows that increasing myofilament function by means of a pH-responsive histidine button engineered into cTnI results in enhanced baseline heart function in Tg mice over their lifetime, and during acute hypoxia improves survival in aged mice by maintaining cardiac contractility.
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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.