TY - JOUR A1 - Chen, Menjia A1 - Liu, Dan A1 - Weidemann, Frank A1 - Lengenfelder, Björn Daniel A1 - Ertl, Georg A1 - Hu, Kai A1 - Frantz, Stefan A1 - Nordbeck, Peter T1 - Echocardiographic risk factors of left ventricular thrombus in patients with acute anterior myocardial infarction JF - ESC Heart Failure N2 - Aims This study aimed to identify echocardiographic determinants of left ventricular thrombus (LVT) formation after acute anterior myocardial infarction (MI). Methods and results This case–control study comprised 55 acute anterior MI patients with LVT as cases and 55 acute anterior MI patients without LVT as controls, who were selected from a cohort of consecutive patients with ischemic heart failure in our hospital. The cases and controls were matched for age, sex, and left ventricular ejection fraction. LVT was detected by routine/contrast echocardiography or cardiac magnetic resonance imaging during the first 3 months following MI. Formation of apical aneurysm after MI was independently associated with LVT formation [72.0% vs. 43.5%, odds ratio (OR) = 5.06, 95% confidence interval (CI) 1.65–15.48, P = 0.005]. Echocardiographic risk factors associated with LVT formation included reduced mitral annular plane systolic excursion (<7 mm, OR = 4.69, 95% CI 1.84–11.95, P = 0.001), moderate–severe diastolic dysfunction (OR = 2.71, 95% CI 1.11–6.57, P = 0.028), and right ventricular (RV) dysfunction [reduced tricuspid annular plane systolic excursion < 17 mm (OR = 5.48, 95% CI 2.12–14.13, P < 0.001), reduced RV fractional area change < 0.35 (OR = 3.32, 95% CI 1.20–9.18, P = 0.021), and enlarged RV mid diameter (per 5 mm increase OR = 1.62, 95% CI 1.12–2.34, P = 0.010)]. Reduced tricuspid annular plane systolic excursion (<17 mm) significantly associated with increased risk of LVT in anterior MI patients (OR = 3.84, 95% CI 1.37–10.75, P = 0.010), especially in those patients without apical aneurysm (OR = 5.12, 95% CI 1.45–18.08, P = 0.011), independent of body mass index, hypertension, anaemia, mitral annular plane systolic excursion, and moderate–severe diastolic dysfunction. Conclusions Right ventricular dysfunction as determined by reduced TAPSE or RV fractional area change is independently associated with LVT formation in acute anterior MI patients, especially in the setting of MI patients without the formation of an apical aneurysm. This study suggests that besides assessment of left ventricular abnormalities, assessment of concomitant RV dysfunction is of importance on risk stratification of LVT formation in patients with acute anterior MI. KW - myocardial infarction KW - aneurysm KW - left ventricular thrombusv KW - right ventricular dysfunction KW - echocardiography KW - cardiovascular magnetic resonance Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261067 VL - 8 IS - 6 ER - TY - JOUR A1 - Kaspar, Mathias A1 - Fette, Georg A1 - Hanke, Monika A1 - Ertl, Maximilian A1 - Puppe, Frank A1 - Störk, Stefan T1 - Automated provision of clinical routine data for a complex clinical follow-up study: A data warehouse solution JF - Health Informatics Journal N2 - A deep integration of routine care and research remains challenging in many respects. We aimed to show the feasibility of an automated transformation and transfer process feeding deeply structured data with a high level of granularity collected for a clinical prospective cohort study from our hospital information system to the study's electronic data capture system, while accounting for study-specific data and visits. We developed a system integrating all necessary software and organizational processes then used in the study. The process and key system components are described together with descriptive statistics to show its feasibility in general and to identify individual challenges in particular. Data of 2051 patients enrolled between 2014 and 2020 was transferred. We were able to automate the transfer of approximately 11 million individual data values, representing 95% of all entered study data. These were recorded in n = 314 variables (28% of all variables), with some variables being used multiple times for follow-up visits. Our validation approach allowed for constant good data quality over the course of the study. In conclusion, the automated transfer of multi-dimensional routine medical data from HIS to study databases using specific study data and visit structures is complex, yet viable. KW - clinical data warehouse KW - clinical study KW - electronic data capture KW - electronic health records KW - secondary data usage Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260828 VL - 28 IS - 1 ER - TY - JOUR A1 - Krieter, Detlef H. A1 - Jeyaseelan, Jarline A1 - Rüth, Marieke A1 - Lemke, Horst-Dieter A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Clinical hemocompatibility of double-filtration lipoprotein apheresis comparing polyethersulfone and ethylene-vinyl alcohol copolymer membranes JF - Artificial Organs N2 - Activation of the complement system and leukocytes by blood–membrane interactions may further promote arteriosclerosis typically present in patients on lipoprotein apheresis. As clinical data on the hemocompatibility of lipoprotein apheresis are scarce, a controlled clinical study comparing two different types of plasma separation and fractionation membranes used in double-filtration lipoprotein apheresis was urgently needed, as its outcome may influence clinical decision-making. In a prospective, randomized, crossover controlled trial, eight patients on double-filtration lipoprotein apheresis were subjected to one treatment with recent polyethersulfone (PES) plasma separation and fractionation membranes and one control treatment using a set of ethylene-vinyl alcohol copolymer (EVAL) membranes. White blood cell (WBC) and platelet (PC) counts, complement factor C5a and thrombin–antithrombin III (TAT) concentrations were determined in samples drawn at defined times from different sites of the extracorporeal blood and plasma circuit. With a nadir at 25 minutes, WBCs in EVAL decreased to 33.5 ± 10.7% of baseline compared with 63.8 ± 22.0% at 20 minutes in PES (P < .001). The maximum C5a levels in venous blood reentering the patients were measured at 30 minutes, being 30.0 ± 11.2 µg/L with EVAL and 12.3 ± 9.0 µg/L with PES (P < .05). The highest C5a concentrations were found in plasma after the plasma filters (EVAL 56.1 ± 22.0 µg/L at 15 minutes vs PES 23.3 ± 15.2 µg/L at 10 minutes; P < .001). PC did not significantly decrease over time with both membrane types, whereas TAT levels did not rise until the end of the treatment without differences between membranes. Regarding lipoprotein(a) and low-density lipoprotein (LDL) cholesterol removal, both membrane sets performed equally. Compared with EVAL, PES membranes cause less leukocyte and complement system activation, the classical parameters of hemocompatibility of extracorporeal treatment procedures, at identical treatment efficacy. Better hemocompatibility may avoid inflammation-promoting effects through blood–material interactions in patients requiring double-filtration lipoprotein apheresis. KW - lipoprotein(a) KW - biocompatibility KW - fractionation membranev KW - hypercholesterolemia KW - LDL cholesterol KW - lipoprotein apheresis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258307 VL - 45 IS - 9 ER - TY - JOUR A1 - Janz, Anna A1 - Zink, Miriam A1 - Cirnu, Alexandra A1 - Hartleb, Annika A1 - Albrecht, Christina A1 - Rost, Simone A1 - Klopocki, Eva A1 - Günther, Katharina A1 - Edenhofer, Frank A1 - Ergün, Süleyman A1 - Gerull, Brenda T1 - CRISPR/Cas9-edited PKP2 knock-out (JMUi001-A-2) and DSG2 knock-out (JMUi001-A-3) iPSC lines as an isogenic human model system for arrhythmogenic cardiomyopathy (ACM) JF - Stem Cell Research N2 - Arrhythmogenic cardiomyopathy (ACM) is characterized by fibro-fatty replacement of the myocardium, heart failure and life-threatening ventricular arrhythmias. Causal mutations were identified in genes encoding for proteins of the desmosomes, predominantly plakophilin-2 (PKP2) and desmoglein-2 (DSG2). We generated gene-edited knock-out iPSC lines for PKP2 (JMUi001-A-2) and DSG2 (JMUi001-A-3) using the CRISPR/Cas9 system in a healthy control iPSC background (JMUi001A). Stem cell-like morphology, robust expression of pluripotency markers, embryoid body formation and normal karyotypes confirmed the generation of high quality iPSCs to provide a novel isogenic human in vitro model system mimicking ACM when differentiated into cardiomyocytes. KW - mutations Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259846 VL - 53 ER - TY - JOUR A1 - Winter, Patrick M. A1 - Andelovic, Kristina A1 - Kampf, Thomas A1 - Hansmann, Jan A1 - Jakob, Peter Michael A1 - Bauer, Wolfgang Rudolf A1 - Zernecke, Alma A1 - Herold, Volker T1 - Simultaneous measurements of 3D wall shear stress and pulse wave velocity in the murine aortic arch JF - Journal of Cardiovascular Magnetic Resonance N2 - Purpose Wall shear stress (WSS) and pulse wave velocity (PWV) are important parameters to characterize blood flow in the vessel wall. Their quantification with flow-sensitive phase-contrast (PC) cardiovascular magnetic resonance (CMR), however, is time-consuming. Furthermore, the measurement of WSS requires high spatial resolution, whereas high temporal resolution is necessary for PWV measurements. For these reasons, PWV and WSS are challenging to measure in one CMR session, making it difficult to directly compare these parameters. By using a retrospective approach with a flexible reconstruction framework, we here aimed to simultaneously assess both PWV and WSS in the murine aortic arch from the same 4D flow measurement. Methods Flow was measured in the aortic arch of 18-week-old wildtype (n = 5) and ApoE\(^{−/−}\) mice (n = 5) with a self-navigated radial 4D-PC-CMR sequence. Retrospective data analysis was used to reconstruct the same dataset either at low spatial and high temporal resolution (PWV analysis) or high spatial and low temporal resolution (WSS analysis). To assess WSS, the aortic lumen was labeled by semi-automatically segmenting the reconstruction with high spatial resolution. WSS was determined from the spatial velocity gradients at the lumen surface. For calculation of the PWV, segmentation data was interpolated along the temporal dimension. Subsequently, PWV was quantified from the through-plane flow data using the multiple-points transit-time method. Reconstructions with varying frame rates and spatial resolutions were performed to investigate the influence of spatiotemporal resolution on the PWV and WSS quantification. Results 4D flow measurements were conducted in an acquisition time of only 35 min. Increased peak flow and peak WSS values and lower errors in PWV estimation were observed in the reconstructions with high temporal resolution. Aortic PWV was significantly increased in ApoE\(^{−/−}\) mice compared to the control group (1.7 ± 0.2 versus 2.6 ± 0.2 m/s, p < 0.001). Mean WSS magnitude values averaged over the aortic arch were (1.17 ± 0.07) N/m\(^2\) in wildtype mice and (1.27 ± 0.10) N/m\(^2\) in ApoE\(^{−/−}\) mice. Conclusion The post processing algorithm using the flexible reconstruction framework developed in this study permitted quantification of global PWV and 3D-WSS in a single acquisition. The possibility to assess both parameters in only 35 min will markedly improve the analyses and information content of in vivo measurements. KW - 4D flow KW - pulse wave velocity KW - wall shear stress KW - radial KW - self-navigation KW - mouse KW - aortic arch KW - atherosclerosis KW - mice KW - flow KW - plaque KW - CMR KW - quantification KW - microscopy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259152 VL - 23 IS - 1 ER - TY - JOUR A1 - Augustin, Anne Marie A1 - Welsch, Stefan A1 - Bley, Thorsten Alexander A1 - Lopau, Kai A1 - Kickuth, Ralph T1 - Color-coded summation images in the evaluation of renal artery stenosis before and after percutaneous transluminal angioplasty JF - BMC Medical Imaging N2 - Background: Endovascular therapy is the gold standard in patients with hemodynamic relevant renal artery stenosis (RAS) resistant to medical therapy. The severity grading of the stenosis as well as the result assessment after endovascular approach is predominantly based on visible estimations of the anatomic appearance. We aim to investigate the application of color-coded DSA parameters to gain hemodynamic information during endovascular renal artery interventions and for the assessment of the procedures technical success. Methods: We retrospectively evaluated 32 patients who underwent endovascular renal artery revascularization and applied color-coded summation imaging on selected monochromatic DSA images. The differences in time to peak (dTTP) of contrast enhancement in predefined anatomical measuring points were analyzed. Furthermore, differences in systolic blood pressure values (SBP) and serum creatinine were obtained. The value of underlying diabetes mellitus as a predictor for clinical outcome was assessed. Correlation analysis between the patients gender as well as the presence of diabetes mellitus and dTTP was performed. Results: Endovascular revascularization resulted in statistically significant improvement in 4/7 regions of interest. Highly significant improvement of perfusion in terms of shortened TTP values could be found at the segmental artery level and in the intrastenotical segment (p<0.001), significant improvement prestenotical and in the apical renal parenchyma (p<0.05). In the other anatomic regions, differences revealed not to be significant. Differences between SBP and serum creatinine levels before and after the procedure were significant (p=0.004 and 0.0004). Patients ' gender as well as the presence of diabetes mellitus did not reveal to be predictors for the clinical success of the procedure. Furthermore, diabetes and gender did not show relevant correlation with dTTP in the parenchymal measuring points. Conclusions: The supplementary use of color-coding DSA and the data gained from parametric images may provide helpful information in the evaluation of the procedures ' technical success. The segmental artery might be a particularly suitable vascular territory for analyzing differences in blood flow characteristics. Further studies with larger cohorts are needed to further confirm the diagnostic value of this technique. KW - digital subtraction angiography KW - color-coded KW - endovascular KW - renal artery KW - PTA Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259086 VL - 21 IS - 1 ER - TY - JOUR A1 - Morbach, Caroline A1 - Beyersdorf, Niklas A1 - Kerkau, Thomas A1 - Ramos, Gustavo A1 - Sahiti, Floran A1 - Albert, Judith A1 - Jahns, Roland A1 - Ertl, Georg A1 - Angermann, Christiane E. A1 - Frantz, Stefan A1 - Hofmann, Ulrich A1 - Störk, Stefan T1 - Adaptive anti-myocardial immune response following hospitalization for acute heart failure JF - ESC Heart Failure N2 - Aims It has been hypothesized that cardiac decompensation accompanying acute heart failure (AHF) episodes generates a pro-inflammatory environment boosting an adaptive immune response against myocardial antigens, thus contributing to progression of heart failure (HF) and poor prognosis. We assessed the prevalence of anti-myocardial autoantibodies (AMyA) as biomarkers reflecting adaptive immune responses in patients admitted to the hospital for AHF, followed the change in AMyA titres for 6 months after discharge, and evaluated their prognostic utility. Methods and results AMyA were determined in n = 47 patients, median age 71 (quartiles 60; 80) years, 23 (49%) female, and 24 (51%) with HF with preserved ejection fraction, from blood collected at baseline (time point of hospitalization) and at 6 month follow-up (visit F6). Patients were followed for 18 months (visit F18). The prevalence of AMyA increased from baseline (n = 21, 45%) to F6 (n = 36, 77%; P < 0.001). At F6, the prevalence of AMyA was higher in patients with HF with preserved ejection fraction (n = 21, 88%) compared with patients with reduced ejection fraction (n = 14, 61%; P = 0.036). During the subsequent 12 months after F6, that is up to F18, patients with newly developed AMyA at F6 had a higher risk for the combined endpoint of death or rehospitalization for HF (hazard ratio 4.79, 95% confidence interval 1.13–20.21; P = 0.033) compared with patients with persistent or without AMyA at F6. Conclusions Our results support the hypothesis that AHF may induce patterns of adaptive immune responses. More studies in larger populations and well-defined patient subgroups are needed to further clarify the role of the adaptive immune system in HF progression. KW - adaptive immune response KW - acute heart failure KW - anti-myocardial KW - autoantibody KW - inflammation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258907 VL - 8 IS - 4 ER - TY - JOUR A1 - Ankenbrand, Markus Johannes A1 - Lohr, David A1 - Schlötelburg, Wiebke A1 - Reiter, Theresa A1 - Wech, Tobias A1 - Schreiber, Laura Maria T1 - Deep learning-based cardiac cine segmentation: Transfer learning application to 7T ultrahigh-field MRI JF - Magnetic Resonance in Medicine N2 - Purpose Artificial neural networks show promising performance in automatic segmentation of cardiac MRI. However, training requires large amounts of annotated data and generalization to different vendors, field strengths, sequence parameters, and pathologies is limited. Transfer learning addresses this challenge, but specific recommendations regarding type and amount of data required is lacking. In this study, we assess data requirements for transfer learning to experimental cardiac MRI at 7T where the segmentation task can be challenging. In addition, we provide guidelines, tools, and annotated data to enable transfer learning approaches by other researchers and clinicians. Methods A publicly available segmentation model was used to annotate a publicly available data set. This labeled data set was subsequently used to train a neural network for segmentation of left ventricle and myocardium in cardiac cine MRI. The network is used as starting point for transfer learning to 7T cine data of healthy volunteers (n = 22; 7873 images) by updating the pre-trained weights. Structured and random data subsets of different sizes were used to systematically assess data requirements for successful transfer learning. Results Inconsistencies in the publically available data set were corrected, labels created, and a neural network trained. On 7T cardiac cine images the model pre-trained on public imaging data, acquired at 1.5T and 3T, achieved DICE\(_{LV}\) = 0.835 and DICE\(_{MY}\) = 0.670. Transfer learning using 7T cine data and ImageNet weight initialization improved model performance to DICE\(_{LV}\) = 0.900 and DICE\(_{MY}\) = 0.791. Using only end-systolic and end-diastolic images reduced training data by 90%, with no negative impact on segmentation performance (DICE\(_{LV}\) = 0.908, DICE\(_{MY}\) = 0.805). Conclusions This work demonstrates and quantifies the benefits of transfer learning for cardiac cine image segmentation. We provide practical guidelines for researchers planning transfer learning projects in cardiac MRI and make data, models, and code publicly available. KW - 7T KW - ultrahigh-field KW - transfer learning KW - segmentation KW - neural networks KW - deep learning KW - cardiac magnetic resonance KW - cardiac function Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257604 VL - 86 IS - 4 ER - TY - THES A1 - Hauser, Tobias Gregor T1 - Mineralocorticoid-receptor antagonism and its metabolic consequences in haemodialysis patients T1 - Mineralkortikoidrezeptorantagonismus und seine metabolischen Folgen in Hämodialysepatienten N2 - Patients on haemodialysis are highly susceptible to different forms of heart failure. To date, the benefit of Mineralocorticoid-receptor antagonist (MRA) administration in haemodialysis patients remains subject to discussion. Biomarkers play an important role in therapy guidance and pose a promising tool to detect pathological processes of heart failure in an earlier stage. The randomised-controlled Mineralocorticoid-Receptor Antagonists in End-Stage Renal Disease (MiREnDa) trial was set up to investigate the effect of 50 mg of spironolactone once daily on left ventricular mass index in haemodialysis patients and several secondary endpoints. This dissertation reports findings from the MiREnDa trial on (a) the efficacy of spironolactone to influence serum levels of biomarkers of heart failure, fibrosis and inflammation and electrolytes and (b) the ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP), Galectin-3 and soluble source of tumorigenicity 2 (sST2) to reflect left ventricular hypertrophy and diastolic dysfunction assessed by imaging characteristics. Treatment of spironolactone over a 40-week period did not alter serum levels of biomarkers of heart failure, fibrosis and inflammation including NT-proBNP, Galectin-3 and sST2. A small but significant effect on serum sodium but not potassium was observed. NT-proBNP was significantly different in the presence or absence of left ventricular hypertrophy (LVH) (normal vs. LVH (median [IQR]): 2,120 [810; 5,040] vs. 6,340 [2,410; 15,360] pg/ml, p<0.01) or moderate and severe diastolic dysfunction (DD) (normal diastolic function and DD grade I vs. DD grade II and DD grade III: 2,300 [850; 6,050] vs. 12,260 [3,340; 34,830] pg/ml, p=0.02). NT-proBNP further showed a significant correlation at baseline with LVMi (Spearman’s rho=0.41, p<0.001), LAVi (Spearman’s rho=0.55, p<0.001) and septal E/e’ (Spearman’s rho=0.45, p<0.001). No correlation was observed between Galectin-3 and the investigated functional and morphological parameters. sST2 was mildly correlated to LVMi at baseline (Spearman’s rho=0.21, p=0.05) and NT-proBNP at baseline (Spearman’s rho=0.37, p<0.001). In conclusion, spironolactone did not affect the investigated parameters but NT-proBNP proved to be significantly correlated to cardiac imaging measurements. N2 - Dialysepatienten erkranken häufig an Formen der Herzinsuffizienz. Zugleich ist der Nutzen von Mineralkortikoidrezeptorantagonisten bei Dialysepatienten bis heute umstritten. Biomarkermessungen ermöglichen es, pathologische Prozesse am Herzen in einem möglichst frühen Stadium zu erkennen. In der randomisiert-kontrollierten "Mineralocorticoid-Receptor Antagonists in End-Stage Renal Disease" (MiREnDa) Studie wurde der Effekt der täglichen Einnahme von 50 mg Spironolacton auf den linksventrikulären Massenindex bei Dialysepatienten zusammen mit verschiedenen sekundären Endpunkten untersucht. Diese Arbeit beleuchtet Ergebnisse der MiREnDa-Studie zur Wirkung von Spironolacton auf Serumspiegel von Biomarkern für Herzinsuffizienz, Fibrose und Entzündung sowie von Elektrolyten. Darüber hinaus wird der Zusammenhang zwischen N-terminalen natriuretischen Peptid Typ B (NT-proBNP), Galectin-3 und Soluble source of tumorigenicity 2 (sST2) und Veränderungen in den wichtigsten bildgebenden Merkmalen linksventrikulärer Hypertrophie und diastolischer Dysfunktion beschrieben. Die Einnahme von Spironolacton über 40 Wochen hatte keinen Effekt auf Biomarker für Herzinsuffizienz, Fibrose und Entzündung wie NT-proBNP, Galectin-3 und sST2. Lediglich die Natriumspiegel, nicht aber die Kaliumspiegel, wurden signifikant beeinflusst. NT-proBNP unterschied sich signifikant zwischen Patient*innen mit und ohne links-ventrikulärer Hypertrophie (LVH) (normal vs. LVH (Median [IQR]): 2.120 [810; 5.040] vs. 6.340 [2.410; 15.360] pg/ml, p<0,01) beziehungsweise mit und ohne relevanter diastolischer Dysfunktion (DD) (normale diastolische Funktion und DD Grad I vs. DD Grad II und DD Grad III: 2.300 [850; 6.050] vs. 12.260 [3.340; 34.830] pg/ml, p=0,02). NT-proBNP korrelierte außerdem signifikant mit LVMi (Spearman's rho=0,41, p<0,001), LAVi (Spearman's rho=0,55, p<0,001) und E/e' (Spearman's rho=0,45, p<0,001). Galectin-3 war unabhängig von allen untersuchten Parametern. sST2 korrelierte mäßig mit LVMi (Spearman's rho=0,21, p=0,05) und deutlich mit NT-proBNP (Spearman's rho=0,37, p<0,001). Zusammenfassend beeinflusste Spironolacton keinen der untersuchten Parameter relevant und lediglich NT-proBNP wies eine signifikante Korrelation zu kardialen Bildgebungsparameters auf. KW - Dialyse KW - Spironolacton KW - Biomarker KW - haemodialysis KW - spironolactone KW - biomarker Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259382 ER - TY - THES A1 - Gaal, Chiara Claudia T1 - Cardiac Antigens and T cell Specificity after Experimental Myocardial Infarction in Mice T1 - Kardiale Antigene und T-Zell Spezifität nach experimentellem Myokardinfarkt in Mäusen N2 - Cardiovascular diseases (CVD), subsuming atherosclerosis of the coronary arteries and subsequent myocardial infarction, are the leading cause of death in the European Union (over 4 million deaths annually), with devastating individual and economic consequences. Recent studies revealed that T cells play a crucial role in post-MI inflammation, healing and remodelling processes. Nevertheless, the specificity profile of adaptive immune responses in the infarcted myocardium has not yet been differentiated. The experiments portrayed in this thesis sought to assess whether post-MI CD4+ T cell responses in mice are triggered by heart specific antigens, and eventually identify relevant epitopes. We were able to create a murine antigen atlas including a list of 206 epitopes for I-Ab and 193 epitopes for I-Ad presented on MHC-II in the context of MI. We sought to consecutively test this panel by in vitro T cell proliferation and antigen recall assays ex vivo. The elispot assay was used as a readout for antigen-specific stimulation by measurement of IL-2 and IFN-γ production, currently the most sensitive approach available to detect even small counts of antigen producing cells. Splenocytes as well as lymphocytes from mediastinal lymph nodes were purified from animals 7 days or 56 days after EMI conducted by ligation of the left anterior descending artery. We were able to provide evidence that post-MI T cell responses in Balb/c mice are triggered by heart-specific antigens and that MYHCA, especially MYHCA614-628, is relevant for that response. Moreover, a significant specific T cell response after MI in C57BL/6J mice was observed for α actin, cardiac muscle 1 [ACTC1], myosin-binding protein C3 [MYBPC3] and myosin heavy chain α [MYHCA] derived heart specific antigens. Generally, the epitopes of interest for Balb/c as well as C57BL/6J could be further investigated and may eventually be modulated in the future. N2 - Herz-Kreislauf-Erkrankungen (CVD) sowie der häufig folgende Myokardinfarkt sind die häufigsten Todesursachen in der Europäischen Union (über 4 Millionen Todesfälle pro Jahr) mit verheerenden individuellen und wirtschaftlichen Folgen. Aktuelle Studien haben gezeigt, dass T-Zellen eine entscheidende Rolle bei Entzündungs-, Heilungs- und Umbauprozessen nach einem Myokardinfarkt spielen. Das Spezifitätsprofil adaptiver Immunantworten im infarzierten Myokard konnte bisher jedoch noch nicht differenziert werden. Die in dieser Arbeit dargestellten Experimente gingen der Frage nach, ob CD4+ T-Zellantworten nach einem Myokardinfarkt in Mäusen durch herzspezifische Antigene ausgelöst werden und ob hieraus relevante Epitope identifiziert werden können. Uns gelang es, einen Maus-Antigen-Atlas zu erstellen, der eine Zusammenstellung von 206 Epitopen für I-Ab und 193 Epitope für I-Ad enthält, welche auf MHC-II im Rahmen des Myokardinfarkts präsentiert werden. Dieses Panel wurde nacheinander durch In-vitro-T-Zell-Proliferations- und Antigen-Recall-Assays ex vivo getestet. Der Elispot-Assay wurde als sensitivster verfügbare Ansatz zur Quantifizierung der antigen-spezifischen Stimulation durch Messung der IL-2- und IFN-γ-Produktion verwendet. Splenozyten sowie Lymphozyten aus mediastinalen Lymphknoten der Mäuse wurden 7 Tage bzw. 56 Tage nach einem experimentellen Myokardinfarkt, welcher durch Ligation der RIVA Arterie durchgeführt wurde, aufgereinigt. Wir konnten nachweisen, dass Post-MI-T-Zellantworten in Balb/c Mäusen durch herzspezifische Antigene ausgelöst werden, und dass MYHCA, insbesondere MYHCA614-628, für diese Antwort relevant ist. Darüber hinaus konnte eine signifikante spezifische T-Zell-Antwort nach Myokardinfarkt in C57BL/6J Mäusen auf aus Alpha-Actin des Herzmuskels 1 [ACTC1], Myosin-bindendes Protein C vom Herztyp [MYBPC3] und der schweren Kette des Myosins α [MYHCA] generierten herzspezifischen Antigenen gezeigt werden. KW - Regulatorische T-Lymphozyt KW - Herzinfarkt KW - Immunreaktion KW - Myosin KW - Kardiologie KW - T-Lymphozyten KW - T-Lymphocytes KW - Myocardial infarction KW - T-Cell Specificity KW - Cardiac Antigens KW - Kardinale Antigene KW - T-Zell Spezifität KW - Myocardial Healing KW - Mycardiale Heilung Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260047 ER -