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1. Cardiomuscular Biomarkers in the Diagnosis and Prognostication of Immune Checkpoint Inhibitor Myocarditis.

Author

Lehmann, Lorenz, Heckmann, Markus, Bailly, Guillaume, Finke, Daniel, Procureur, Adrien, Power, John, Stein, Frederic, Bretagne, Marie, Ederhy, Stephane, Fenioux, Charlotte, Hamwy, Omar, Funck-Brentano, Elisa, Romano, Emanuela, Pieroni, Laurence, Münster, Jan, Allenbach, Yves, Anquetil, Céline, Leonard-Louis, Sarah, Palaskas, Nicolas, Hayek, Salim, Katus, Hugo, Giannitsis, Evangelos, Frey, Norbert, Kaya, Ziya, Moslehi, Javid, Prifti, Edi, and Salem, Joe-Elie

Subjects
biomarkers, drug-related side effects and adverse reactions, immune checkpoint inhibitors, myocarditis, pharmacology, troponins, Humans, Myocarditis, Immune Checkpoint Inhibitors, Biomarkers, Creatine Kinase, Prognosis, Troponin T
Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. METHODS: We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. RESULTS: Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P=0.03 versus cTnT), and 43 of 57 ([75%] P

Published
2023

2. Prediction of diagnosis and diastolic filling pressure by AI-enhanced cardiac MRI: a modelling study of hospital data

Author

Lehmann, David Hermann, primary, Gomes, Bruna, additional, Vetter, Niklas, additional, Braun, Olivia, additional, Amr, Ali, additional, Hilbel, Thomas, additional, Müller, Jens, additional, Köthe, Ulrich, additional, Reich, Christoph, additional, Kayvanpour, Elham, additional, Sedaghat-Hamedani, Farbod, additional, Meder, Manuela, additional, Haas, Jan, additional, Ashley, Euan, additional, Rottbauer, Wolfgang, additional, Felbel, Dominik, additional, Bekeredjian, Raffi, additional, Mahrholdt, Heiko, additional, Keller, Andreas, additional, Ong, Peter, additional, Seitz, Andreas, additional, Hund, Hauke, additional, Geis, Nicolas, additional, André, Florian, additional, Engelhardt, Sandy, additional, Katus, Hugo A, additional, Frey, Norbert, additional, Heuveline, Vincent, additional, and Meder, Benjamin, additional

Published
2024
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3. Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes

Author

Stamatelopoulos, Kimon, Mueller-Hennessen, Matthias, Georgiopoulos, Georgios, Lopez-Ayala, Pedro, Sachse, Marco, Vlachogiannis, Nikolaos I., Sopova, Kateryna, Delialis, Dimitrios, Bonini, Francesca, Patras, Raphael, Ciliberti, Giorgia, Vafaie, Mehrshad, Biener, Moritz, Boeddinghaus, Jasper, Nestelberger, Thomas, Koechlin, Luca, Tual-Chalot, Simon, Kanakakis, Ioannis, Gatsiou, Aikaterini, Katus, Hugo, Spyridopoulos, Ioakim, Mueller, Christian, Giannitsis, Evangelos, and Stellos, Konstantinos

Published
2022
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6. NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart

Author

Müller, Marion, Eghbalian, Rose, Boeckel, Jes-Niels, Frese, Karen S., Haas, Jan, Kayvanpour, Elham, Sedaghat-Hamedani, Farbod, Lackner, Maximilian K., Tugrul, Oguz F., Ruppert, Thomas, Tappu, Rewati, Martins Bordalo, Diana, Kneuer, Jasmin M., Piekarek, Annika, Herch, Sabine, Schudy, Sarah, Keller, Andreas, Grammes, Nadja, Bischof, Cornelius, Klinke, Anna, Cardoso-Moreira, Margarida, Kaessmann, Henrik, Katus, Hugo A., Frey, Norbert, Steinmetz, Lars M., and Meder, Benjamin

Published
2022
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7. Skeletal muscle derived Musclin protects the heart during pathological overload

Author

Szaroszyk, Malgorzata, Kattih, Badder, Martin-Garrido, Abel, Trogisch, Felix A., Dittrich, Gesine M., Grund, Andrea, Abouissa, Aya, Derlin, Katja, Meier, Martin, Holler, Tim, Korf-Klingebiel, Mortimer, Völker, Katharina, Garfias Macedo, Tania, Pablo Tortola, Cristina, Boschmann, Michael, Huang, Nora, Froese, Natali, Zwadlo, Carolin, Malek Mohammadi, Mona, Luo, Xiaojing, Wagner, Michael, Cordero, Julio, Geffers, Robert, Batkai, Sandor, Thum, Thomas, Bork, Nadja, Nikolaev, Viacheslav O., Müller, Oliver J., Katus, Hugo A., El-Armouche, Ali, Kraft, Theresia, Springer, Jochen, Dobreva, Gergana, Wollert, Kai C., Fielitz, Jens, von Haehling, Stephan, Kuhn, Michaela, Bauersachs, Johann, and Heineke, Joerg

Published
2022
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10. A Self-Taught Artificial Agent for Multi-Physics Computational Model Personalization

Author

Neumann, Dominik, Mansi, Tommaso, Itu, Lucian, Georgescu, Bogdan, Kayvanpour, Elham, Sedaghat-Hamedani, Farbod, Amr, Ali, Haas, Jan, Katus, Hugo, Meder, Benjamin, Steidl, Stefan, Hornegger, Joachim, and Comaniciu, Dorin

Subjects
Computer Science - Computational Engineering, Finance, and Science, Computer Science - Artificial Intelligence
Abstract

Personalization is the process of fitting a model to patient data, a critical step towards application of multi-physics computational models in clinical practice. Designing robust personalization algorithms is often a tedious, time-consuming, model- and data-specific process. We propose to use artificial intelligence concepts to learn this task, inspired by how human experts manually perform it. The problem is reformulated in terms of reinforcement learning. In an off-line phase, Vito, our self-taught artificial agent, learns a representative decision process model through exploration of the computational model: it learns how the model behaves under change of parameters. The agent then automatically learns an optimal strategy for on-line personalization. The algorithm is model-independent; applying it to a new model requires only adjusting few hyper-parameters of the agent and defining the observations to match. The full knowledge of the model itself is not required. Vito was tested in a synthetic scenario, showing that it could learn how to optimize cost functions generically. Then Vito was applied to the inverse problem of cardiac electrophysiology and the personalization of a whole-body circulation model. The obtained results suggested that Vito could achieve equivalent, if not better goodness of fit than standard methods, while being more robust (up to 11% higher success rates) and with faster (up to seven times) convergence rate. Our artificial intelligence approach could thus make personalization algorithms generalizable and self-adaptable to any patient and any model., Comment: Submitted to Medical Image Analysis, Elsevier

Published
2016

13. Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas

Author

Gitsioudis, Gitsios, Chatzizisis, Yiannis S, Wolf, Peter, Missiou, Anna, Antoniadis, Antonios P, Mitsouras, Dimitrios, Bartling, Sönke, Arica, Zeynep, Stuber, Matthias, Rybicki, Frank J, Nunninger, Max, Erbel, Christian, Libby, Peter, Giannoglou, George D, Katus, Hugo A, and Korosoglou, Grigorios

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Biomedical Imaging, Atherosclerosis, Bioengineering, Animals, Aorta, Biopsy, Needle, Computed Tomography Angiography, Confidence Intervals, Disease Models, Animal, Disease Progression, Endothelium, Vascular, Hyperlipidemias, Immunohistochemistry, Inflammation, Linear Models, Magnetic Resonance Imaging, Male, Molecular Imaging, Observer Variation, Plaque, Atherosclerotic, Predictive Value of Tests, ROC Curve, Rabbits, Random Allocation, Reproducibility of Results, Sensitivity and Specificity, Shear Strength, Ultrasonography, Interventional, atherosclerosis, hyperlipidaemic rabbits, endothelial shear stress, molecular imaging, magnetic resonance imaging, computed tomography angiography, Cardiovascular medicine and haematology
Abstract

AimsTo evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque.Methods and resultsTwelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001).ConclusionLow ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.

Published
2017

14. Insulin resistance in Takotsubo syndrome.

Author

Bruns, Bastian, Joos, Maximilian, Elsous, Nesrin, Katus, Hugo A., Schultz, Jobst‐Hendrik, Frey, Norbert, Backs, Johannes, and Meder, Benjamin

Subjects
MYOCARDIAL infarction, BLOOD sugar, MANN Whitney U Test, INSULIN therapy, VENTRICULAR ejection fraction, INSULIN resistance
Abstract

Aims: Takotsubo syndrome (TTS) is an acute heart failure (AHF) syndrome mimicking the symptoms of acute myocardial infarction. Impaired outcome has been shown, making risk stratification and novel therapeutic concepts a necessity. We hypothesized insulin resistance with elevated plasma glucose and potentially myocardial glucose deprivation to contribute to the pathogenesis of TTS and investigated the therapeutic benefit of insulin in vivo. Methods and results: First, we retrospectively analysed patient data of n = 265 TTS cases (85.7% female, mean age 71.1 ± 14.1 years) with documented initial plasma glucose from the Department of Cardiology of the University Hospital Heidelberg in Germany (May 2011 to May 2021). Median split of the study population according to glucose levels (≤123 mg/dL vs. >123 mg/dL) yielded significantly elevated mean heart rate (80.75 ± 18.96 vs. 90.01 ± 22.19 b.p.m., P < 0.001), left ventricular end‐diastolic pressure (LVEDP, 18.51 ± 8.35 vs. 23.09 ± 7.97 mmHg, P < 0.001), C‐reactive protein (26.14 ± 43.30 vs. 46.4 ± 68.6 mg/L, P = 0.006), leukocyte count (10.12 ± 4.29 vs. 15.05 ± 9.83/nL, P < 0.001), peak high‐sensitive Troponin T (hs‐TnT, 515.44 ± 672.15 vs. 711.40 ± 736.37 pg/mL, P = 0.005), reduced left ventricular ejection fraction (EF, 34.92 ± 8.94 vs. 31.35 ± 8.06%, P < 0.001), and elevated intrahospital mortality (2.3% vs. 12.1%, P = 0.002) in the high‐glucose group (Student's t‐test, Mann–Whitney U test, or chi‐squared test). Linear regression indicated a significant association of glucose with HR (P < 0.001), LVEDP (P = 0.014), hs‐TnT kinetics from admission to the next day (P < 0.001), hs‐TnT the day after admission (P < 0.001), as well as peak hsTnT (P < 0.001). Logistic regression revealed significant association of glucose with a composite intrahospital outcome including catecholamine use, respiratory support, and resuscitation [OR 1.010 (1.004–1.015), P = 0.001]. To further investigate the potential role of glucose in TTS pathophysiology experimentally, we utilized an in vivo murine model of epinephrine (EPI)‐driven reversible AHF. For this, male mice underwent therapeutic injection of insulin (INS, 1 IU/kg) or/and glucose (GLU, 0.5 g/kg) after EPI (2.5 mg/kg), both of which markedly improved mean EF (EPI 34.3% vs. EPI + INS + GLU 43.7%, P = 0.025) and significantly blunted mean hs‐TnT (EPI 14 393 pg/mL vs. EPI + INS 6864 pg/mL at 24 h, P = 0.039). Particularly, insulin additionally ameliorated myocardial pro‐inflammatory gene expression, suggesting an anti‐inflammatory effect of acute insulin therapy. Conclusions: Elevated initial plasma glucose was associated with adverse outcome‐relevant parameters in TTS and may present a surrogate parameter of heightened catecholaminergic drive. In mice, insulin‐ and glucose injection both improved EPI‐induced AHF and myocardial damage, indicating insulin resistance rather than detrimental effects of hyperglycaemia itself as the underlying cause. Future studies will investigate the role of HbA1c as a risk stratifier and of insulin‐based therapy in TTS. [ABSTRACT FROM AUTHOR]

Published
2024
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18. A complex intervention to promote prevention of delirium in older adults by targeting caregiver’s participation during and after hospital discharge – study protocol of the TRAnsport and DElirium in older people (TRADE) project

Author

Leinert, Christoph, Brefka, Simone, Braisch, Ulrike, Denninger, Natascha, Mueller, Martin, Benzinger, Petra, Bauer, Juergen, Bahrmann, Anke, Frey, Norbert, Katus, Hugo A., Geisler, Tobias, Eschweiler, Gerhard, Klaus, Jochen, Seufferlein, Thomas, Schuetze, Konrad, Gebhard, Florian, Dreyhaupt, Jens, Muche, Rainer, Pahmeier, Kathrin, Biermann-Stallwitz, Janine, Wasem, Juergen, Flagmeier, Lena, Dallmeier, Dhayana, and Denkinger, Michael

Published
2021
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23. CAT score single item analysis in patients with COPD: Results from COSYCONET

Author

Stefan, Andreas, Robert, Bals, Jürgen, Behr, Kathrin, Kahnert, Burkhard, Bewig, Roland, Buhl, Ralf, Ewert, Beate, Stubbe, Ficker, Joachim H., Manfred, Gogol, Christian, Grohé, Rainer, Hauck, Matthias, Held, Berthold, Jany, Markus, Henke, Felix, Herth, Gerd, Höffken, Katus Hugo, A., Anne-Marie, Kirsten, Henrik, Watz, Rembert, Koczulla, Klaus, Kenn, Juliane, Kronsbein, Cornelia, Kropf-Sanchen, Christoph, Lange, Peter, Zabel, Michael, Pfeifer, Randerath Winfried, J., Werner, Seeger, Michael, Studnicka, Christian, Taube, Helmut, Teschler, Hartmut, Timmermann, Christian, Virchow J., Claus, Vogelmeier, Ulrich, Wagner, Tobias, Welte, Hubert, Wirtz, Lehnert, Doris, Struck, Birte, Krabbe, Lenka, Arikan, Barbara, Tobias, Julia, Speth, Kornelia, Pieper, Jeanette, Gleiniger, Margret, Markworth, Britta, Hinz, Zaklina, Burmann, Ellen, Wons, Katrin, Rieber, Ulrike, Schaufler, Beate, Schwedler, Katrin, Michalewski, Sabine, Rohweder, Sonja, Berger, Patricia, Schottel, Diana, Janke, Vivien, Untsch, Rosalie, Graf, Jana, Reichel, Anita, Weiß, Gertraud, Traugott, Erich, Kietzmann, Ilona, Schrade-Illmann, Michaela, Polte, Beate, Hübner, Gudrun, Marietta von Siemens, Sarah, Alter, Peter, Lutter, Johanna I., Kauczor, Hans-Ulrich, Jobst, Bertram, Bals, Robert, Trudzinski, Franziska C., Söhler, Sandra, Behr, Jürgen, Watz, Henrik, Waschki, Benjamin, Bewig, Burkhard, Jones, Paul W., Welte, Tobias, Vogelmeier, Claus F., Jörres, Rudolf A., and Kahnert, Kathrin

Published
2019
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24. 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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25. 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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26. 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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27. Long-Term Prognosis of Patients With Takotsubo Syndrome

Author

Ghadri, Jelena R., Kato, Ken, Cammann, Victoria L., Gili, Sebastiano, Jurisic, Stjepan, Di Vece, Davide, Candreva, Alessandro, Ding, Katharina J., Micek, Jozef, Szawan, Konrad A., Bacchi, Beatrice, Bianchi, Rahel, Levinson, Rena A., Wischnewsky, Manfred, Seifert, Burkhardt, Schlossbauer, Susanne A., Citro, Rodolfo, Bossone, Eduardo, Münzel, Thomas, Knorr, Maike, Heiner, Susanne, D’Ascenzo, Fabrizio, Franke, Jennifer, Sarcon, Annahita, Napp, L. Christian, Jaguszewski, Milosz, Noutsias, Michel, Katus, Hugo A., Burgdorf, Christof, Schunkert, Heribert, Thiele, Holger, Bauersachs, Johann, Tschöpe, Carsten, Pieske, Burkert M., Rajan, Lawrence, Michels, Guido, Pfister, Roman, Cuneo, Alessandro, Jacobshagen, Claudius, Hasenfuß, Gerd, Karakas, Mahir, Koenig, Wolfgang, Rottbauer, Wolfgang, Said, Samir M., Braun-Dullaeus, Ruediger C., Banning, Adrian, Cuculi, Florim, Kobza, Richard, Fischer, Thomas A., Vasankari, Tuija, Airaksinen, K.E. Juhani, Opolski, Grzegorz, Dworakowski, Rafal, MacCarthy, Philip, Kaiser, Christoph, Osswald, Stefan, Galiuto, Leonarda, Crea, Filippo, Dichtl, Wolfgang, Empen, Klaus, Felix, Stephan B., Delmas, Clément, Lairez, Olivier, El-Battrawy, Ibrahim, Akin, Ibrahim, Borggrefe, Martin, Horowitz, John, Kozel, Martin, Tousek, Petr, Widimský, Petr, Gilyarova, Ekaterina, Shilova, Alexandra, Gilyarov, Mikhail, Winchester, David E., Ukena, Christian, Bax, Jeroen J., Prasad, Abhiram, Böhm, Michael, Lüscher, Thomas F., Ruschitzka, Frank, and Templin, Christian

Published
2018
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29. Editor's Choice – 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)

Author

Aboyans, Victor, Ricco, Jean-Baptiste, Bartelink, Marie-Louise E.L., Björck, Martin, Brodmann, Marianne, Cohnert, Tina, Collet, Jean-Philippe, Czerny, Martin, De Carlo, Marco, Debus, Sebastian, Espinola-Klein, Christine, Kahan, Thomas, Kownator, Serge, Mazzolai, Lucia, Naylor, A. Ross, Roffi, Marco, Röther, Joachim, Sprynger, Muriel, Tendera, Michal, Tepe, Gunnar, Venermo, Maarit, Vlachopoulos, Charalambos, Desormais, Ileana, Document Reviewers, Widimsky, Petr, Kolh, Philippe, Agewall, Stefan, Bueno, Héctor, Coca, Antonio, De Borst, Gert J., Delgado, Victoria, Dick, Florian, Erol, Cetin, Ferrini, Marc, Kakkos, Stavros, Katus, Hugo A., Knuuti, Juhani, Lindholt, Jes, Mattle, Heinrich, Pieniazek, Piotr, Piepoli, Massimo Francesco, Scheinert, Dierk, Sievert, Horst, Simpson, Iain, Sulzenko, Jakub, Tamargo, Juan, Tokgozoglu, Lale, Torbicki, Adam, Tsakountakis, Nikolaos, Tuñón, José, Vega de Ceniga, Melina, Windecker, Stephan, and Zamorano, Jose Luis

Published
2018
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31. 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

32. 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

36. Abstract 686: Glp-2 Predicts Cardiovascular Outcomes In Patients With Myocardial Infarction And Increases Atherosclerosis In Mice

Author

Sausen, Maximillian, primary, Mertens, Robert, additional, Quintana, Luis, additional, Rueckbeil, Marcia, additional, Idel, Paul, additional, Tabaza, Nadim, additional, Ganesh, Naresh, additional, Just, Susanne, additional, Arrivas, Maria, additional, Moellmann, Julia, additional, Spießhoefer, Jens, additional, Biener, Moritz B, additional, Giannitsis, Evangelos, additional, Katus, Hugo, additional, Drucker, Daniel J, additional, Marx, Nikolaus, additional, Lehrke, Michael, additional, and Kahles, Florian, additional

Published
2023
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37. 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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42. 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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44. Basophils balance healing after myocardial infarction via IL-4/IL-13

Author

Sicklinger, Florian, Meyer, Ingmar Soren, Li, Xue, Radtke, Daniel, Dicks, Severin, Kornadt, Moritz P., Mertens, Christina, Meier, Julia K., Lavine, Kory J., Zhang, Yunhang, Kuhn, Tim Christian, Terzer, Tobias, Patel, Jyoti, Boerries, Melanie, Schramm, Gabriele, Frey, Norbert, Katus, Hugo A., Voehringer, David, and Leuschner, Florian

Subjects
Heart attack -- Development and progression, Inflammation -- Development and progression, Regeneration (Biology) -- Health aspects -- Physiological aspects, Interleukin-13 -- Health aspects -- Physiological aspects, Basophils -- Health aspects -- Physiological aspects, Interleukin-4 -- Health aspects -- Physiological aspects, Health care industry
Abstract

The inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7 Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative [Ly6C.sup.lo] macrophages toward increased numbers of inflammatory [Ly6C.sup.hi] monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were accompanied by lower cardiac levels of IL-4 and IL-13, two major cytokines secreted by basophils. Mice with basophil-specific IL-4/IL-13 deficiency exhibited a similarly altered myeloid response with an increased fraction of [Ly6C.sup.hi] monocytes and aggravated cardiac function after MI. In contrast, IL-4 induction in basophils via administration of the glycoprotein IPSE/[alpha]-1 led to improved post-MI healing. These results in mice were corroborated by the finding that initially low counts of blood basophils in patients with acute MI were associated with a worse cardiac outcome after 1 year, characterized by a larger scar size. In conclusion, we show that basophils promoted tissue repair after MI by increasing cardiac IL-4 and IL-13 levels., Introduction Inflammation is an essential mechanism for restoring tissue integrity after myocardial infarction (MI). After restriction of blood supply, the inflammatory response is characterized by a multistep cascade at both [...]

Published
2021
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45. 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

48. 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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49. 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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