scholarly journals Abnormal splicing in the N-terminal variable region of cardiac troponin T impairs systolic function of the heart with preserved Frank-Starling compensation

2014 ◽  
Vol 2 (9) ◽  
pp. e12139 ◽  
Author(s):  
Han-Zhong Feng ◽  
Guozhen Chen ◽  
Changlong Nan ◽  
Xupei Huang ◽  
Jian-Ping Jin
Keyword(s):  
Cardiac Troponin ◽  
Troponin T ◽  
Systolic Function ◽  
Variable Region ◽  
Cardiac Troponin T

Increased levels of cardiac troponin-T in outpatients with heart failure and preserved systolic function are related to adverse clinical findings and outcome

2006 ◽  
Vol 17 (8) ◽  
pp. 685-691 ◽  
Author(s):  
Stella M. Macin ◽  
Eduardo R. Perna ◽  
Juan P. Cimbaro Canella ◽  
Natalia Augier ◽  
Jorge L. Riera Stival ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Systolic Function ◽  
Clinical Findings ◽  
Cardiac Troponin T

Prognostic value of combination of NT-proBNP and cardiac troponin T in patients admitted for CHF with preserved LV systolic function

2008 ◽  
Vol 14 (7) ◽  
pp. S151
Author(s):  
Hiroyuki Naruse ◽  
Junnichi Ishii ◽  
Kousuke Hattori ◽  
Makoto Ishikawa ◽  
Masanori Okumura ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Prognostic Value ◽  
Troponin T ◽  
Systolic Function ◽  
Cardiac Troponin T ◽  
Lv Systolic Function

scholarly journals Myopathic Splice-Out of the Exon 7 segment of Cardiac Troponin T Predominantly Impairs Systolic Function of the Heart

2011 ◽  
Vol 100 (3) ◽  
pp. 452a
Author(s):  
Hanzhong Feng ◽  
Guozhen Chen ◽  
Changlong Nan ◽  
J.-P. Jin
Keyword(s):  
Cardiac Troponin ◽  
Troponin T ◽  
Systolic Function ◽  
Cardiac Troponin T

Abstract 62: Cardiac Troponin T Isoform Switching in Early Childhood Tropomyosin-linked Dilated Cardiomyopathy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Melissa Lynn ◽  
Lauren Tal-Grinspan ◽  
J.-P. Jin ◽  
Jil Tardiff
Keyword(s):  
Mouse Model ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Systolic Function ◽  
Phenotypic Variability ◽  
Bimodal Distribution ◽  
General Mechanism ◽  
Cardiac Troponin T ◽  
Human Heart Failure

An oft-noted component of sarcomeric DCM is the observation that patients within families carrying the same primary mutation exhibit significant phenotypic variability. This lack of a distinct link between genotype and phenotype has complicated clinical management. In a recent study of two unrelated multigenerational families with the tropomyosin (Tm) mutation Asp230Asn (D230N), a striking “bimodal” distribution of severity was observed. In these families, many children (<1 year) with the mutation presented with a severe form of DCM that led to sudden, often fatal CHF while adults developed a mild to moderate DCM in mid-life. Of note, children who survived the initial presentation often recovered significant systolic function into young adulthood. A potential hypothesis to explain this improvement despite the continued presence of the mutant Tm, is that the phenotype is modified by other thin filament isoforms. Thus we propose that the age-dependent remodeling seen in children with D230N Tm is a result of temporal isoform switches involving a closely linked Tm binding partner cardiac Troponin T (cTnT). Our initial biophysical studies (Regulated-IVM) revealed a decreased Ca2+ sensitivity in filaments containing D230N Tm that is more severe in the presence of fetal TnT (cTnT1), suggesting a modulatory role for cTnT1. Cardiac performance, assessed via 2D echo, in our novel D230N Tm x cTnT1 double transgenic (DTg) mouse model found a significantly reduced % FS for DTg (17%) mice as compared to D230N Tm (21%) littermates. This reduction in %FS was seen at 4 months but not 2 suggesting a progressive cardiomyopathy. Current efforts aim to model the early phase of this “bimodal” phenotype and assess the potential for disease reversibility using a cardiac specific inducible cTnT1 transgenic mouse model. Furthermore, we propose that modulation by cTnT1 could represent a more general mechanism for the progressive remodeling seen in human heart failure. Preliminary in vitro studies with human tissue found that RNA levels of cTnT1 are significantly higher in failing hearts as compared to non-failing. Thus these data suggest an isoform dependent mechanism for the “bimodal” phenotype in patients carrying D230N Tm that could translate to other sarcomeric cardiomyopathies.

Expression of cardiac troponin T with COOH-terminal truncation accelerates cross-bridge interaction kinetics in mouse myocardium

2004 ◽  
Vol 287 (4) ◽  
pp. H1756-H1761 ◽  
Author(s):  
Julian E. Stelzer ◽  
Jitandrakumar R. Patel ◽  
M. Charlotte Olsson ◽  
Daniel P. Fitzsimons ◽  
Leslie A. Leinwand ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Thin Filament ◽  
Troponin T ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Hill Coefficient ◽  
Cardiac Troponin T ◽  
Cross Bridge ◽  
Interaction Kinetics ◽  
Filament Activation

Transgenic mice expressing an allele of cardiac troponin T (cTnT) with a COOH-terminal truncation (cTnTtrunc) exhibit severe diastolic and mild systolic dysfunction. We tested the hypothesis that contractile dysfunction in myocardium expressing low levels of cTnTtrunc (i.e., <5%) is due to slowed cross-bridge kinetics and reduced thin filament activation as a consequence of reduced cross-bridge binding. We measured the Ca2+ sensitivity of force development [pCa for half-maximal tension generation (pCa50)] and the rate constant of force redevelopment ( ktr) in cTnTtrunc and wild-type (WT) skinned myocardium both in the absence and in the presence of a strong-binding, non-force-generating derivative of myosin subfragment-1 (NEM-S1). Compared with WT mice, cTnTtrunc mice exhibited greater pCa50, reduced steepness of the force-pCa relationship [Hill coefficient ( nH)], and faster ktr at submaximal Ca2+ concentration ([Ca2+]), i.e., reduced activation dependence of ktr. Treatment with NEM-S1 elicited similar increases in pCa50 and similar reductions in nH in WT and cTnTtrunc myocardium but elicited greater increases in ktr at submaximal activation in cTnTtrunc myocardium. Contrary to our initial hypothesis, cTnTtrunc appears to enhance thin filament activation in myocardium, which is manifested as significant increases in Ca2+-activated force and the rate of cross-bridge attachment at submaximal [Ca2+]. Although these mechanisms would not be expected to depress systolic function per se in cTnTtrunc hearts, they would account for slowed rates of myocardial relaxation during early diastole.

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