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109. Ventrikuläre Extrasystolen und Breitkomplextachykardien

Author

Berkovitz, Artur, Deneke, Thomas, Ene, Elena, Halbfaß, Philipp, Hebe, Joachim, Hobbiesiefken, Sven, Katus, Hugo A., Konrad, Torsten, Lange, Björn, Marx, Alexandra, Nentwich, Karin, Neuzner, Jörg, Paliege, Robert, Reinhardt, Adrian, Rostock, Thomas, Siebels, Jürgen, Scholz, Eberhard P., and Sonne, Kai

Published
2019
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113. miR-10 Regulates Angiogenesis through VEGF Signaling Titration

Author

Hassel, David, Katus, Hugo A, Stainier, Didier Y, and Srivastava, Deepak

Subjects
Vascular development, Angiogenesis, Cell signaling, Cardiovascular System & Hematology, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Public Health and Health Services
Published
2012

114. MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling.

Author

Hassel, David, Cheng, Paul, White, Mark, Ivey, Kathryn, Kroll, Jens, Augustin, Hellmut, Katus, Hugo, Stainier, Didier, and Srivastava, Deepak

Subjects
Animals, Animals, Genetically Modified, Base Sequence, Cell Proliferation, Cells, Cultured, Endothelial Cells, Female, Gene Knockdown Techniques, Green Fluorescent Proteins, Human Umbilical Vein Endothelial Cells, Humans, Immunoblotting, Larva, Male, Mice, MicroRNAs, Microscopy, Confocal, Neovascularization, Physiologic, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Nucleic Acid, Signal Transduction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2, Zebrafish
Abstract

RATIONALE: Formation and remodeling of the vasculature during development and disease involve a highly conserved and precisely regulated network of attractants and repellants. Various signaling pathways control the behavior of endothelial cells, but their posttranscriptional dose titration by microRNAs is poorly understood. OBJECTIVE: To identify microRNAs that regulate angiogenesis. METHODS AND RESULTS: We show that the highly conserved microRNA family encoding miR-10 regulates the behavior of endothelial cells during angiogenesis by positively titrating proangiogenic signaling. Knockdown of miR-10 led to premature truncation of intersegmental vessel growth in the trunk of zebrafish larvae, whereas overexpression of miR-10 promoted angiogenic behavior in zebrafish and cultured human umbilical venous endothelial cells. We found that miR-10 functions, in part, by directly regulating the level of fms-related tyrosine kinase 1 (FLT1), a cell-surface protein that sequesters vascular endothelial growth factor, and its soluble splice variant sFLT1. The increase in FLT1/sFLT1 protein levels upon miR-10 knockdown in zebrafish and in human umbilical venous endothelial cells inhibited the angiogenic behavior of endothelial cells largely by antagonizing vascular endothelial growth factor receptor 2 signaling. CONCLUSIONS: Our study provides insights into how FLT1 and vascular endothelial growth factor receptor 2 signaling is titrated in a microRNA-mediated manner and establishes miR-10 as a potential new target for the selective modulation of angiogenesis.

Published
2012

118. Modification of the GRACE Risk Score for Risk Prediction in Patients With Acute Coronary Syndromes

Author

Georgiopoulos, Georgios, primary, Kraler, Simon, additional, Mueller-Hennessen, Matthias, additional, Delialis, Dimitrios, additional, Mavraganis, Georgios, additional, Sopova, Kateryna, additional, Wenzl, Florian A., additional, Räber, Lorenz, additional, Biener, Moritz, additional, Stähli, Barbara E., additional, Maneta, Eleni, additional, Spray, Luke, additional, Iglesias, Juan F., additional, Coelho-Lima, Jose, additional, Tual-Chalot, Simon, additional, Muller, Olivier, additional, Mach, François, additional, Frey, Norbert, additional, Duerschmied, Daniel, additional, Langer, Harald F., additional, Katus, Hugo, additional, Roffi, Marco, additional, Camici, Giovanni G., additional, Mueller, Christian, additional, Giannitsis, Evangelos, additional, Spyridopoulos, Ioakim, additional, Lüscher, Thomas F., additional, Stellos, Konstantinos, additional, and Stamatelopoulos, Kimon, additional

Published
2023
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119. Abstract P3040: Development Of A Protein Synthesis Network At The Sarcoplasmic Reticulum In Adult Cardiomyocytes

Author

Hofmann, Christoph, primary, Brandenburg, Sören, additional, Uhlenkamp, Dennis, additional, Meyer, Bianca, additional, Sandmann, Clara, additional, Herzog, Nicole, additional, Groß, Julia, additional, Sramek, Viviana, additional, Renz, Marc, additional, Katus, Hugo A, additional, Lehnart, Stephan E, additional, Völkers, Mirko, additional, and Doroudgar, Shirin, additional

Published
2023
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120. Prognosis of light chain amyloidosis: a multivariable analysis for survival prediction in patients with cardiac involvement proven by endomyocardial biopsy

Author

Aurich, Matthias, primary, Bucur, Julian, additional, Vey, Johannes A, additional, Greiner, Sebastian, additional, aus dem Siepen, Fabian, additional, Hegenbart, Ute, additional, Schönland, Stefan, additional, Katus, Hugo A, additional, Frey, Norbert, additional, and Mereles, Derliz, additional

Published
2023
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122. Dual Functional States of R406W-Desmin Assembly Complexes Cause Cardiomyopathy With Severe Intercalated Disc Derangement in Humans and in Knock-In Mice

Author

Herrmann, Harald, Cabet, Eva, Chevalier, Nicolas R., Moosmann, Julia, Schultheis, Dorothea, Haas, Jan, Schowalter, Mirjam, Berwanger, Carolin, Weyerer, Veronika, Agaimy, Abbas, Meder, Benjamin, Müller, Oliver J., Katus, Hugo A., Schlötzer-Schrehardt, Ursula, Vicart, Patrick, Ferreiro, Ana, Dittrich, Sven, Clemen, Christoph S., Lilienbaum, Alain, and Schröder, Rolf

Published
2020
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131. Relevance of pre-analytical blood management on the emerging cardiovascular protein biomarkers TWEAK and HMGB1 and on miRNA serum and plasma profiling

Author

Basso, Daniela, Padoan, Andrea, Laufer, Thomas, Aneloni, Vittorio, Moz, Stefania, Schroers, Hannah, Pelloso, Michela, Saiz, Anna, Krapp, Medea, Fogar, Paola, Cornoldi, Paola, Zambon, Carlo-Federico, Rossi, Elisa, La Malfa, Marco, Marotti, Alberto, Brefort, Thomas, Weis, Tanja M., Katus, Hugo A., and Plebani, Mario

Published
2017
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133. PRediction of acute coronary syndrome in acute ischemic StrokE (PRAISE) – protocol of a prospective, multicenter trial with central reading and predefined endpoints

Author

Nolte, Christian H., von Rennenberg, Regina, Litmeier, Simon, Scheitz, Jan F., Leistner, David M., Blankenberg, Stephan, Dichgans, Martin, Katus, Hugo, Petzold, Gabor C., Pieske, Burkert, Regitz-Zagrosek, Vera, Wegscheider, Karl, Zeiher, Andreas M., Landmesser, Ulf, and Endres, Matthias

Published
2020
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135. S100A1: A Regulator of Myocardial Contractility

Author

Most, Patrick, Bernotat, Juliane, Ehlermann, Philipp, Pleger, Sven T., Reppel, Michael, Börries, Melanie, Niroomand, Ferraydoon, Pieske, Burkert, Eschenhagen, Thomas, Karczewski, Peter, Smith, Godfrey L., Koch, Walter J., Katus, Hugo A., and Remppis, Andrew

Published
2001

136. Cardiological parameters predict mortality and cardiotoxicity in oncological patients.

Author

Romann, Sebastian W., Finke, Daniel, Heckmann, Markus B., Hund, Hauke, Giannitsis, Evangelos, Katus, Hugo A., Frey, Norbert, and Lehmann, Lorenz H.

Subjects
BRAIN natriuretic factor, CANCER patients, CARDIOTOXICITY, CARDIOVASCULAR diseases risk factors, VENTRICULAR ejection fraction
Abstract

Aims: Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient‐related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all‐cause mortality (ACM) and the development of cardiotoxicity. Methods and results: Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio‐Oncology Unit at the Heidelberg University Hospital were included. They were evaluated by medical history, physical examination, 12‐lead electrocardiogram, 2D echocardiography, and cardiac biomarkers [high‐sensitivity cardiac troponin T (hs‐cTnT) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP)]. The primary endpoint was defined as ACM and the secondary endpoint was defined as cardiotoxicity, as defined by the European Society of Cardiology. Of the 1971 patients enrolled, the primary endpoint was reached by 490 patients (25.7%) with a median of 363.5 [interquartile range (IQR) 121.8, 522.5] days after presentation. Hs‐cTnT of ≥ 7 ng/L [odds ratio (OR) 1.82, P < 0.001] and NT‐proBNP (OR 1.98, P < 0.001) were independent predictors of ACM, while reduced left ventricular ejection fraction was not associated with increased ACM (P = 0.85). The secondary endpoint was reached by 182 patients (9.2%) with a median of 793.5 [IQR 411.2, 1165.0] days. Patients with multiple CVRFs (defined as high risk, n = 886) had an increased risk of cardiotoxicity (n = 100/886, 11.3%; hazard ratio 1.57, P = 0.004). They showed elevated baseline values of hs‐cTnT (OR 1.60, P = 0.006) and NT‐proBNP (OR 4.00, P < 0.001) and had an increased risk of ACM (OR 1.43, P = 0.031). Conclusions: In cancer patients, CVRF accumulation predicts cardiotoxicity whereas elevated hs‐cTnT or NT‐proBNP levels are associated with ACM. Accordingly, less intensive surveillance protocols may be warranted in patients with low cardiac biomarker levels and absence of CVRFs. [ABSTRACT FROM AUTHOR]

Published
2024
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137. Acute changes in cardiac dimensions, function, and longitudinal mechanics in healthy individuals with and without high‐altitude induced pulmonary hypertension at 4559 m.

Author

Mereles, Derliz, Rudolph, Jens, Greiner, Sebastian, Aurich, Matthias, Frey, Norbert, Katus, Hugo A., Bärtsch, Peter, and Dehnert, Christoph

Subjects
ECHOCARDIOGRAPHY, BLOOD pressure, LEFT heart ventricle, PULMONARY hypertension, PULMONARY artery, GLOBAL longitudinal strain, MOUNTAIN sickness, COMPARATIVE studies, DOPPLER echocardiography, CARDIAC output, RESEARCH funding, HEART physiology, HYPOXEMIA, PHENOTYPES
Abstract

Background: High‐altitude pulmonary hypertension (HAPH) has a prevalence of approximately 10%. Changes in cardiac morphology and function at high altitude, compared to a population that does not develop HAPH are scarce. Methods: Four hundred twenty‐one subjects were screened in a hypoxic chamber inspiring a FiO2 = 12% for 2 h. In 33 subjects an exaggerated increase in systolic pulmonary artery pressure (sPAP) could be confirmed in two independent measurements. Twenty nine of these, and further 24 matched subjects without sPAP increase were examined at 4559 m by Doppler echocardiography including global longitudinal strain (GLS). Results: SPAP increase was higher in HAPH subjects (∆ = 10.2 vs. ∆ = 32.0 mm Hg, p <.001). LV eccentricity index (∆ =.15 vs. ∆ =.31, p =.009) increased more in HAPH. D‐shaped LV (0 [0%] vs. 30 [93.8%], p =.00001) could be observed only in the HAPH group, and only in those with a sPAP ≥50 mm Hg. LV‐EF (∆ = 4.5 vs. ∆ = 6.7%, p =.24) increased in both groups. LV‐GLS (∆ = 1.2 vs. ∆ = 1.1 –%, p =.60) increased slightly. RV end‐diastolic (∆ = 2.20 vs. ∆ = 2.7 cm2, p =.36) and end‐systolic area (∆ = 2.1 vs. ∆ = 2.7 cm2, p =.39), as well as RA end‐systolic area index (∆ = −.9 vs. ∆ =.3 cm2/m2, p =.01) increased, RV‐FAC (∆ = −2.9 vs. ∆ = −4.7%, p =.43) decreased, this was more pronounced in HAPH, RV‐GLS (∆ = 1.6 vs. ∆ = −.7 –%, p =.17) showed marginal changes. Conclusions: LV and LA dimensions decrease and left ventricular function increases at high‐altitude in subjects with and without HAPH. RV and RA dimensions increase, and RV longitudinal strain increases or remains unchanged in subjects with HAPH. Changes are negligible in those without HAPH. [ABSTRACT FROM AUTHOR]

Published
2024
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142. CITED4 Protects Against Adverse Remodeling in Response to Physiological and Pathological Stress

Author

Lerchenmüller, Carolin, Rabolli, Charles P., Yeri, Ashish, Kitchen, Robert, Salvador, Ane M., Liu, Laura X., Ziegler, Olivia, Danielson, Kirsty, Platt, Colin, Shah, Ravi, Damilano, Federico, Kundu, Piyusha, Riechert, Eva, Katus, Hugo A., Saffitz, Jeffrey E., Keshishian, Hasmik, Carr, Steven A., Bezzerides, Vassilios J., Das, Saumya, and Rosenzweig, Anthony

Published
2020
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143. Heart-Specific Immune Responses in an Animal Model of Autoimmune-Related Myocarditis Mitigated by an Immunoproteasome Inhibitor and Genetic Ablation

Author

Bockstahler, Mariella, Fischer, Andrea, Goetzke, Carl Christoph, Neumaier, Hannah Louise, Sauter, Martina, Kespohl, Meike, Müller, Anna-Maria, Meckes, Christin, Salbach, Christian, Schenk, Mirjam, Heuser, Arnd, Landmesser, Ulf, Weiner, January, Meder, Benjamin, Lehmann, Lorenz, Kratzer, Adelheid, Klingel, Karin, Katus, Hugo A., Kaya, Ziya, and Beling, Antje

Published
2020
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145. Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry

Author

Ding, Katharina J., Cammann, Victoria L., Szawan, Konrad A., Stähli, Barbara E., Wischnewsky, Manfred, Di Vece, Davide, Citro, Rodolfo, Jaguszewski, Milosz, Seifert, Burkhardt, Sarcon, Annahita, Knorr, Maike, Heiner, Susanne, Gili, Sebastiano, D’Ascenzo, Fabrizio, Neuhaus, Michael, Napp, L. Christian, Franke, Jennifer, Noutsias, Michel, Burgdorf, Christof, Koenig, Wolfgang, Kherad, Behrouz, Rajan, Lawrence, Michels, Guido, Pfister, Roman, Cuneo, Alessandro, Jacobshagen, Claudius, Karakas, Mahir, Pott, Alexander, Meyer, Philippe, Arroja, Jose D., Banning, Adrian, Cuculi, Florim, Kobza, Richard, Fischer, Thomas A., Vasankari, Tuija, Airaksinen, K.E. Juhani, Paolini, Carla, Bilato, Claudio, Carrilho-Ferreira, Pedro, Opolski, Grzegorz, Dworakowski, Rafal, MacCarthy, Philip, Kaiser, Christoph, Osswald, Stefan, Galiuto, Leonarda, Dichtl, Wolfgang, Chan, Christina, Bridgman, Paul, Delmas, Clément, Lairez, Olivier, El-Battrawy, Ibrahim, Akin, Ibrahim, Gilyarova, Ekaterina, Shilova, Alexandra, Gilyarov, Mikhail, Kozel, Martin, Tousek, Petr, Widimský, Petr, Winchester, David E., Galuszka, Jan, Ukena, Christian, Horowitz, John D., Di Mario, Carlo, Prasad, Abhiram, Rihal, Charanjit S., Pinto, Fausto J., Crea, Filippo, Borggrefe, Martin, Braun-Dullaeus, Ruediger C., Rottbauer, Wolfgang, Bauersachs, Johann, Katus, Hugo A., Hasenfuß, Gerd, Tschöpe, Carsten, Pieske, Burkert M., Thiele, Holger, Schunkert, Heribert, Böhm, Michael, Felix, Stephan B., Münzel, Thomas, Bax, Jeroen J., Lüscher, Thomas F., Ruschitzka, Frank, Ghadri, Jelena R., Bossone, Eduardo, and Templin, Christian

Published
2020
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148. A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway

Author

Lehmann, Lorenz H, Jebessa, Zegeye H, Kreusser, Michael M, Horsch, Axel, He, Tao, Kronlage, Mariya, Dewenter, Matthias, Sramek, Viviana, Oehl, Ulrike, Krebs-Haupenthal, Jutta, von der Lieth, Albert H, Schmidt, Andrea, Sun, Qiang, Ritterhoff, Julia, Finke, Daniel, Völkers, Mirko, Jungmann, Andreas, Sauer, Sven W, Thiel, Christian, Nickel, Alexander, Kohlhaas, Michael, Schäfer, Michaela, Sticht, Carsten, Maack, Christoph, Gretz, Norbert, Wagner, Michael, El-Armouche, Ali, Maier, Lars S, Londoño, Juan E Camacho, Meder, Benjamin, Freichel, Marc, Gröne, Hermann-Josef, Most, Patrick, Müller, Oliver J, Herzig, Stephan, Furlong, Eileen E M, Katus, Hugo A, and Backs, Johannes

Subjects
Heart failure -- Prevention -- Research, Quantitative trait loci -- Research, Gene expression -- Research, Histones -- Physiological aspects -- Research, Biological sciences, Health
Abstract

The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure., Author(s): Lorenz H Lehmann [1, 2, 3]; Zegeye H Jebessa [1, 2]; Michael M Kreusser [1, 2, 3]; Axel Horsch [1, 2]; Tao He [1, 2]; Mariya Kronlage [1, 2, [...]

Published
2018
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149. Vito – A Generic Agent for Multi-physics Model Personalization: Application to Heart Modeling

Author

Neumann, Dominik, Mansi, Tommaso, Itu, Lucian, Georgescu, Bogdan, Kayvanpour, Elham, Sedaghat-Hamedani, Farbod, Haas, Jan, Katus, Hugo, Meder, Benjamin, Steidl, Stefan, Hornegger, Joachim, Comaniciu, Dorin, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Navab, Nassir, editor, Hornegger, Joachim, editor, Wells, William M., editor, and Frangi, Alejandro, editor

Published
2015
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150. Estimation of Regional Electrical Properties of the Heart from 12-Lead ECG and Images

Author

Seegerer, Philipp, Mansi, Tommaso, Jolly, Marie-Pierre, Neumann, Dominik, Georgescu, Bogdan, Kamen, Ali, Kayvanpour, Elham, Amr, Ali, Sedaghat-Hamedani, Farbod, Haas, Jan, Katus, Hugo, Meder, Benjamin, Comaniciu, Dorin, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Camara, Oscar, editor, Mansi, Tommaso, editor, Pop, Mihaela, editor, Rhode, Kawal, editor, Sermesant, Maxime, editor, and Young, Alistair, editor

Published
2015
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