cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform

2005 ◽  
Vol 288 (3) ◽  
pp. H1147-H1156 ◽  
Author(s):  
Rashid Nassar ◽  
Nadia N. Malouf ◽  
Lan Mao ◽  
Howard A. Rockman ◽  
Annette E. Oakeley ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Cardiac Troponin T ◽  
Force Development ◽  
Amino Terminal

Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium-dependent myocardial force development, are expressed in the human; they differ in charge and length. Their expression is regulated developmentally and is affected by disease states. Human cTnT (hcTnT) isoform effects have been examined in reconstituted myofilaments. In this study, we evaluated the modulatory effects of overexpressing one cTnT isoform on in vitro and in vivo myocardial function. A hcTnT isoform, hcTnT1, expressed during development and in heart disease but not in the normal adult heart, was expressed in transgenic (TG) mice (1–30% of total cTnT). Maximal active tension measured in skinned myocardium decreased as a function of relative hcTnT1 expression. The pCa at half-maximal force development, Hill coefficient, and rate of redevelopment of force did not change significantly with hcTnT1 expression. In vivo maximum rates of rise and fall of left ventricular pressure decreased, and the half-time of isovolumic relaxation increased, with hcTnT1 expression. Substituting total cTnT charge for hcTnT1 expression resulted in similar conclusions. Morphometric analysis and electron microscopy revealed no differences between wild-type (non-TG) and TG myocardium. No differences in isoform expression of tropomyosin, myosin heavy chain, essential and regulatory myosin light chains (MLC), TnI, or in posttranslational modifications of mouse cTnT, cTnI, or regulatory MLC were observed. These results support the hypothesis that cTnT isoform amino-terminal differences affect myofilament function and suggest that hcTnT1 expression levels present during human development and in human heart disease can affect in vivo ventricular function.

scholarly journals Coexistence of cardiac troponin T variants reduces heart efficiency

2010 ◽  
Vol 299 (1) ◽  
pp. H97-H105 ◽  
Author(s):  
Han-Zhong Feng ◽  
J.-P. Jin
Keyword(s):  
Cardiac Muscle ◽  
Transgenic Mouse ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Ex Vivo ◽  
Heart Function ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Troponin T ◽  
Myofilament Activation

Corresponding to the synchronized contraction of the myocardium and rhythmic pumping function of the heart, a single form of cardiac troponin T (cTnT) is present in the adult cardiac muscle of humans and most other vertebrate species. Alternative splicing variants of cTnT are found in failing human hearts and animal dilated cardiomyopathies. Biochemical analyses have shown that these cTnT variants are functional and produce shifted myofilament Ca2+ sensitivity. We proposed a hypothesis that the coexistence of two or more functionally distinct TnT variants in the adult ventricular muscle that is normally activated as a syncytium may decrease heart function and cause cardiomyopathy (Huang et al., Am J Physiol Cell Physiol 294: C213–C222, 2008). In the present study, we studied transgenic mouse hearts expressing one or two cTnT variants in addition to normal adult cTnT to investigate whether desynchronized myofilament activation decreases ventricular efficiency. The function of ex vivo working hearts was examined in the absence of systemic neurohumoral influence. The results showed that the transgenic mouse hearts produced lower maximum left ventricular pressure, slower contractile and relaxation velocities, and decreased stroke volume compared with wild-type controls. Ventricular pumping efficiency, calculated by the ejection integral versus total systolic integral and cardiac work versus oxygen consumption, was significantly lower in transgenic mouse hearts and corresponded to the number of cTnT variants present. The results indicated a pathogenic mechanism in which the coexistence of functionally different cTnT variants in cardiac muscle reduces myocardial efficiency due to desynchronized thin filament activation.

scholarly journals Cardiac troponin I, cardiac troponin T, and creatine kinase MB in dialysis patients without ischemic heart disease: evidence of cardiac troponin T expression in skeletal muscle

1997 ◽  
Vol 43 (6) ◽  
pp. 976-982 ◽  
Author(s):  
Mary D McLaurin ◽  
Fred S Apple ◽  
Ellen M Voss ◽  
Charles A Herzog ◽  
Scott W Sharkey
Keyword(s):  
Skeletal Muscle ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Cardiac Troponin ◽  
First Generation ◽  
Troponin T ◽  
Ischemic Heart ◽  
Cardiac Troponin T ◽  
Dialysis Patients ◽  
Acute Ischemic Heart Disease

Abstract Serum cardiac troponin T (cTnT) concentrations are frequently increased in chronic dialysis patients as measured by the first-generation ELISA immunoassay, as is creatine kinase (CK) MB mass in the absence of acute ischemic heart disease. We designed this study to compare four serum markers of myocardial injury [CK-MB mass, first-generation ELISA cTnT, second-generation Enzymun cTnT, and cardiac troponin I (cTnI)] in dialysis patients without acute ischemic heart disease. We also evaluated skeletal muscle from dialysis patients as a potential source of serum cTnT. No patients in the clinical evaluation group (n = 24) studied by history and by physical examination, electrocardiography, and two-dimensional echocardiography had evidence of ischemic heart disease. Biochemical markers were measured in serial predialysis blood samples with specific monoclonal antibody-based immunoassays. For several patients at least one sample measured above the upper reference limit: CK-MB, 7 of 24 (30%); ELISA cTnT, 17 of 24 (71%); Enzymun cTnT, 3 of 18 (17%); and cTnI, 1 of 24 (4%). In a separate group of dialysis patients (n = 5), expression of cTnT, but not cTnI, was demonstrated by Western blot analysis in 4 of 5 skeletal muscle biopsies. Chronic dialysis patients without acute ischemic heart disease frequently had increased serum CK-MB and cTnT. The specificity of the second-generation cTnT (Enzymun) assay was improved over that of the first-generation (ELISA) assay; cTnI was the most specific of the currently available biochemical markers. cTnT, but not cTnI, was expressed in the skeletal muscle of dialysis patients.

In vivo safety and accuracy of a clinically applicable telemetered left ventricular pressure module: intermediate-term results

2004 ◽  
Vol 10 (4) ◽  
pp. S67 ◽  
Author(s):  
Patrick I. McConnell ◽  
Daise de Cunha ◽  
Tanya Shipkowitz ◽  
Justin Van Hee ◽  
Phillip H. Long ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure

scholarly journals Left Ventricular Pressure-Volume Characteristics in Congenital Heart Disease

Circulation ◽  
1968 ◽  
Vol 37 (6) ◽  
pp. 879-889 ◽  
Author(s):  
M. M. JARMAKANI ◽  
SAM B. EDWARDS ◽  
MADISON S. SPACH ◽  
RAMON V. CANENT ◽  
M. PAUL CAPP ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Volume Characteristics

scholarly journals Prognostic Value of Combination of Cardiac Troponin T and B-Type Natriuretic Peptide after Initiation of Treatment in Patients with Chronic Heart Failure

2003 ◽  
Vol 49 (12) ◽  
pp. 2020-2026 ◽  
Author(s):  
Junnichi Ishii ◽  
Wei Cui ◽  
Fumihiko Kitagawa ◽  
Takahiro Kuno ◽  
Yuu Nakamura ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Functional Class ◽  
Cardiac Troponin T ◽  
Cardiac Events ◽  
Nyha Functional Class

Abstract Background: Recent studies have suggested that cardiac troponin T (cTnT) and troponin I may detect ongoing myocardial damage involved in the progression of chronic heart failure (CHF). This study was prospectively designed to examine whether the combination of cTnT, a marker for ongoing myocardial damage, and B-type natriuretic peptide (BNP), a marker for left ventricular overload, would effectively stratify patients with CHF after initiation of treatment. Methods: We measured serum cTnT, plasma BNP, and left ventricular ejection fraction (LVEF) on admission for worsening CHF [New York Heart Association (NYHA) functional class III to IV] and 2 months after initiation of treatment to stabilize CHF (n = 100; mean age, 68 years). Results: Mean (SD) concentrations of cTnT [0.023 (0.066) vs 0.063 (0.20) μg/L] and BNP [249 (276) vs 753 (598) ng/L], percentage increased cTnT (>0.01 μg/L; 35% vs 60%), NYHA functional class [2.5 (0.6) vs 3.5 (5)], and LVEF [43 (13)% vs 36 (12)%] were significantly (P <0.01) improved 2 months after treatment compared with admission. During a mean follow-up of 391 days, there were 44 cardiac events, including 12 cardiac deaths and 32 readmissions for worsening CHF. On a stepwise Cox regression analysis, increased cTnT and BNP were independent predictors of cardiac events (P <0.001). cTnT >0.01 μg/L and/or BNP >160 ng/L 2 months after initiation of treatment were associated with increased cardiac mortality and morbidity rates. Conclusion: The combination of cTnT and BNP measurements after initiation of treatment may be highly effective for risk stratification in patients with CHF.

Abstract 3809: Cardiac-Specific Overexpression of EcSOD Using an AAV9 Vector in Combination with the Cardiac Troponin-T Promoter Inhibits LV Remodeling after Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Konkal-Matt R Prasad ◽  
Ronald J Beyers ◽  
Yaqin Xu ◽  
Brent A French
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Left Ventricular ◽  
The Body ◽  
Cardiac Troponin T ◽  
Sod Activity ◽  
Western Blots ◽  
Systemic Injection ◽  
Lv Remodeling

Introduction: The wide tissue tropism exhibited by AAV provides for efficient gene transfer throughout the body, but targeting gene expression to cardiomyocytes is desirable for cardiac gene therapy. We hypothesized that targeted overexpression of extracellular superoxide dismutase (EcSOD) via the cardiac Troponin-T (cTnT) promoter would suffice to minimize left ventricular (LV) remodeling after myocardial infarction (MI). Methods: An AAV9 vector expressing EcSOD from the cTnT promoter (AcTnTEcSOD) was injected into 5 wk-old C57 mice via jugular vein (3x10 11 vp/mouse). Western blots, immunohistochemistry & in vitro SOD assays were used to measure EcSOD expression, distribution and activity. Cardiac magnetic resonance (CMR) imaging was performed at baseline (5 wks post-vector injection) and at days 1, 7 & 28 after MI to assess LV volumes (vol) & ejection fraction (EF) as compared to WT mice (n=4). Infarct (IF) sizes were also compared by DE on D1. Results: Systemic injection of the vector (AcTnTEcSOD) provided uniform EcSOD overexpression within cardiomyocytes (Panels A&B) and elevated total cardiac SOD activity by 5.6 fold (p<0.05). On D1 post-MI, IF sizes were similar in vector & WT groups (p=ns). The vector group had significantly lower end-diastolic vol at D7, D28 and lower end-systolic vol at D28 (all p<0.05 by ANOVA, Panels C&D), resulting in improved D28 EF over controls (p=0.02). Conclusions: Cardiac-specific overexpression of therapeutic genes can be achieved by combining highly-efficient AAV9 vectors with cardiac-specific promoters. AAV-mediated, cardiac-restricted overexpression of EcSOD from the cTnT promoter significantly reduces post-MI LV remodeling.

Factors associated with baseline and serial changes in circulating NT-proBNP and high-sensitivity cardiac troponin T in a population-based cohort (Dallas Heart Study)

2021 ◽  
Author(s):  
Christopher W Puleo ◽  
Colby R Ayers ◽  
Sonia Garg ◽  
Ian J Neeland ◽  
Alana A Lewis ◽  
...  
Keyword(s):  
Body Composition ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Left Ventricular ◽  
Cardiac Troponin T ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Heart Study ◽  
Dallas Heart Study

Aim: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) associate with structural heart disease and heart failure risk in individuals without known cardiovascular disease (CVD). However, few data are available regarding whether factors influencing levels of these two biomarkers are similar or distinct. We performed serial measurement of NT-proBNP and hs-cTnT in a contemporary multiethnic cohort with extensive phenotyping, with the goal of identifying their respective biological determinants in a population without known or suspected CVD. Methods: We evaluated 1877 participants of the Dallas Heart Study who had NT-proBNP and hs-cTnT measured and were free from clinical CVD at the each of its two examinations (2000–2002 and 2007–2009). Variables collected included demographic and risk factors, high-sensitivity C-reactive protein, body composition via dual-energy x-ray absorptiometry, coronary artery calcium by computed tomography, and cardiac dimensions and function by cardiac MRI. Linear regression was used to identify associations of these factors with each biomarker at baseline and with changes in biomarkers over follow-up. Results: NT-proBNP and hs-cTnT were poorly correlated at baseline (Spearman rho 0.083, p = 0.015), with only moderate correlation between change values (rho 0.18, p < 0.001). hs-cTnT positively associated and NT-proBNP inversely associated with male gender and black race. At baseline, both NT-proBNP and hs-cTnT associated with left ventricular end-diastolic volume and wall thickness, but only NT-proBNP associated with left atrial size. Changes in cardiac dimensions between phases were more strongly associated with changes in NT-proBNP than hs-cTnT. NT-proBNP was more strongly associated with high-sensitivity C-reactive protein and measures of body composition than hs-cTnT. Conclusion: Among individuals without CVD in the general population, NT-proBNP and hs-cTnT are nonredundant biomarkers that are differentially associated with demographic and cardiac factors. These findings indicate that hs-cTnT and NT-proBNP may reflect different pathophysiological pathways.

scholarly journals Increased cardiac troponin T and endothelin-1 concentrations in dialysis patients may indicate heart disease

1999 ◽  
Vol 14 (8) ◽  
pp. 1948-1955 ◽  
Author(s):  
Christian Löwbeer ◽  
Astrid Ottosson-Seeberger ◽  
Sven A. Gustafsson ◽  
Rolf Norrman ◽  
Johan Hulting ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Cardiac Troponin T ◽  
Dialysis Patients ◽  
Endothelin 1

scholarly journals Altered ventricular mechanics after 60 min of high-intensity endurance exercise: insights from exercise speckle-tracking echocardiography

2015 ◽  
Vol 308 (8) ◽  
pp. H875-H883 ◽  
Author(s):  
Glenn M. Stewart ◽  
Akira Yamada ◽  
Luke J. Haseler ◽  
Justin J. Kavanagh ◽  
Gus Koerbin ◽  
...  
Keyword(s):  
Mean Arterial Pressure ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Left Ventricular ◽  
Cardiac Troponin T ◽  
Low Intensity ◽  
Exercise Challenge ◽  
Exercise Induced ◽  
Low Intensity Exercise

Transient reductions in myocardial strain coupled with cardiac-specific biomarker release have been reported after prolonged exercise (>180 min). However, it is unknown if 1) shorter-duration exercise (60 min) can perturb cardiac function or 2) if exercise-induced reductions in strain are masked by hemodynamic changes that are associated with passive recovery from exercise. Left ventricular (LV) and right ventricular global longitudinal strain (GLS), LV torsion, and high-sensitivity cardiac troponin T were measured in 15 competitive cyclists (age: 28 ± 3 yr, peak O2 uptake: 4.8 ± 0.6 l/min) before and after a 60-min high-intensity cycling race intervention (CRIT60). At both time points (pre- and post-CRIT60), strain and torsion were assessed at rest and during a standardized low-intensity exercise challenge (power output: 96 ± 8 W) in a semirecumbent position using echocardiography. During rest, hemodynamic conditions were different from pre- to post-CRIT60 (mean arterial pressure: 96 ± 1 vs. 86 ± 2 mmHg, P < 0.001), and there were no changes in strain or torsion. In contrast, during the standardized low-intensity exercise challenge, hemodynamic conditions were unchanged from pre- to post-CRIT60 (mean arterial pressure: 98 ± 1 vs. 97 ± 1 mmHg, not significant), but strain decreased (left ventricular GLS: −20.3 ± 0.5% vs. −18.5 ± 0.4%, P < 0.01; right ventricular GLS: −26.4 ± 1.6% vs. −22.4 ± 1.5%, P < 0.05), whereas LV torsion remained unchanged. Serum high-sensitivity cardiac troponin T increased by 345% after the CRIT60 (6.0 ± 0.6 vs. 20.7 ± 6.9 ng/l, P < 0.05). This study demonstrates that exercise-induced functional and biochemical cardiac perturbations are not confined to ultraendurance sporting events and transpire during exercise that is typical of day-to-day training undertaken by endurance athletes. The clinical significance of cumulative exposure to endurance exercise warrants further study.

Sign in / Sign up

Export Citation Format

Share Document