scholarly journals A single direct injection into the left ventricular wall of an adeno-associated virus 9 (AAV9) vector expressing extracellular superoxide dismutase from the cardiac troponin-T promoter protects mice against myocardial infarction

2011 ◽  
Vol 13 (6) ◽  
pp. 333-341 ◽  
Author(s):  
Konkal-Matt R. Prasad ◽  
Robert S. Smith ◽  
Yaqin Xu ◽  
Brent A French
Keyword(s):  
Myocardial Infarction ◽  
Superoxide Dismutase ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Direct Injection ◽  
Left Ventricular ◽  
Cardiac Troponin T ◽  
Ventricular Wall ◽  
Extracellular Superoxide Dismutase ◽  
Adeno Associated Virus

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.

scholarly journals Single-Point Cardiac Troponin T at Coronary Care Unit Discharge after Myocardial Infarction Correlates with Infarct Size and Ejection Fraction

2002 ◽  
Vol 48 (9) ◽  
pp. 1432-1436 ◽  
Author(s):  
Mauro Panteghini ◽  
Claudio Cuccia ◽  
Graziella Bonetti ◽  
Raffaele Giubbini ◽  
Franca Pagani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Cardiac Troponin ◽  
Coronary Care Unit ◽  
Troponin T ◽  
Left Ventricular ◽  
Lv Function ◽  
Cardiac Troponin T ◽  
Coronary Care

Abstract Background: One of the major concerns in replacing creatine kinase MB (CK-MB) with cardiac troponins is the lack of evidence of the ability of troponins to estimate the size of acute myocardial infarction (AMI). We investigated the ability of a single measurement of cardiac troponin T (cTnT) at coronary care unit (CCU) discharge to estimate infarct size and assess left ventricular (LV) function in AMI patients. Methods: We studied 65 AMI patients in whom infarct size was estimated by CK-MB peak concentrations and gated single-photon emission computed tomography (SPECT) myocardial perfusion using technetium-99m sestamibi and LV function by SPECT imaging. Measurements of cTnT and SPECT were performed 72 h (median) after admission (range, 40–160 h). SPECT was also repeated 3 months later. Results: We found a significant correlation between cTnT and both the peak CK-MB concentrations (r = 0.76; P &lt;0.001) and the perfusion defect size at SPECT (r = 0.62; P &lt;0.001). cTnT was inversely related to LV ejection fraction (LVEF) assessed both early (r = −0.56; P &lt;0.001) and 3 months after AMI (r = −0.70; P &lt;0.001). cTnT &gt;2.98 μg/L predicted a LVEF &lt;40% at 3 months with a sensitivity of 86.7%, specificity of 81.4%, and a likelihood ratio for a positive test of 4.7 (95% confidence interval, 4.0–5.4). Conclusions: A single cTnT measurement at CCU discharge after AMI is useful as a noninvasive estimate of infarct size and for the assessment of LV function in routine clinical setting.

scholarly journals Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e052004
Author(s):  
Alexander Dietl ◽  
Martina E Zimmermann ◽  
Caroline Brandl ◽  
Stefan Wallner ◽  
Ralph Burkhardt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Left Ventricular ◽  
Cardiac Troponin T ◽  
Cross Sectional ◽  
Reference Limit ◽  
Mobile Population ◽  
Upper Reference Limit

ObjectiveEuropean guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age.DesignA cross-sectional analysis was performed in the German AugUR study (Altersbezogene Untersuchungen zur Gesundheit der University of Regensburg).SettingStudy population was the mobile population aged 70+ years living in the city and county of Regensburg, Germany.ParticipantsA random sample was derived from the local population registries of residence. Of the 5644 individuals invited, 1133 participated (response ratio=20.1%). All participants came to the study centre and were mentally and physically mobile to conduct the protocol (face-to-face interview, blood draw and standardised transthoracic echocardiography). None of the participants was in an acute state of myocardial infarction.ResultsAmong the 1129 individuals with hsTnT measurements (overall median=10.0 ng/L(25th, 75th percentile)=(7.0, 15.0 ng/L)), hsTnT was higher among the older individuals and higher among men (men 70–74 years median=9.6 ng/L (7.2, 13.1 ng/L); men 90–95 years median=21.2 ng/L (14.6, 26.0 ng/L); women 70–74 years median=6.3 ng/L (4.7, 8.7 ng/L); and women 90–95 years median=18.0 ng/L (11.0, 21.0 ng/L)). In participants with impaired kidney function (eGFRcrea <60 mL/min/1.73 m2), hsTnT was elevated (median=13.6 ng/L (9.4, 20.6 ng/L)).Specificity of recommended upper reference limit, 14 ng/L, is 68%. Most false positives were among men aged >79 years (specificity=34%). In a healthy subgroup (n=96, none of the following: overt heart disease, impaired renal function, blood pressure >160/100 mm Hg, left ventricular hypertrophy and diastolic/systolic dysfunction), specificity was 90%.ConclusionIn the elderly population without acute myocardial infarction, hsTnT further increases with age showing different levels for men and women. The specificity of the 14 ng/L cut-off is considerably lower than 99%, even in healthy subjects.

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