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2. Effect of inferior caval valve implantation on circulating immune cells and inflammatory mediators in severe tricuspid regurgitation.

Author

Mattig, Isabel, Hewing, Bernd, Knebel, Fabian, Meisel, Christian, Ludwig, Antje, Konietschke, Frank, Stangl, Verena, Stangl, Karl, Laule, Michael, and Dreger, Henryk

Subjects
INFLAMMATORY mediators, KILLER cells, VENA cava inferior, TUMOR necrosis factors, CYTOTOXIC T cells, TRICUSPID valve insufficiency
Abstract

Background: Interventional valve implantation into the inferior vena cava (CAVI) lowers venous congestion in patients with tricuspid regurgitation (TR). We evaluated the impact of a reduction of abdominal venous congestion following CAVI on circulating immune cells and inflammatory mediators. Methods: Patients with severe TR were randomized to optimal medical therapy (OMT) + CAVI (n = 8) or OMT (n = 10). In the OMT + CAVI group, an Edwards Sapien XT valve was implanted into the inferior vena cava. Immune cells and inflammatory mediators were measured in the peripheral blood at baseline and three-month follow-up. Results: Leukocytes, monocytes, basophils, eosinophils, neutrophils, lymphocytes, B, T and natural killer cells and inflammatory markers (C-reactive protein, interferon-gamma, interleukin-2, -4, -5, -10, and tumor necrosis factor-alpha) did not change substantially between baseline and three-month follow-up within the OMT + CAVI and OMT group. Conclusion: The present data suggest that reduction of venous congestion following OMT + CAVI may not lead to substantial changes in systemic inflammation within a short-term follow-up. Clinical trial registration: NCT02387697 [ABSTRACT FROM AUTHOR]

Published
2024
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5. A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study

Author

Reinecke, Holger, primary, Engelbertz, Christiane, additional, Bauersachs, Rupert, additional, Breithardt, Günter, additional, Echterhoff, Hans-Herbert, additional, Gerß, Joachim, additional, Haeusler, Karl Georg, additional, Hewing, Bernd, additional, Hoyer, Joachim, additional, Juergensmeyer, Sabine, additional, Klingenheben, Thomas, additional, Knapp, Guido, additional, Christian Rump, Lars, additional, Schmidt-Guertler, Hans, additional, Wanner, Christoph, additional, Kirchhof, Paulus, additional, and Goerlich, Dennis, additional

Published
2023
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10. A Randomized Controlled Trial Comparing Apixaban to the Vitamin K-antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 study.

Author

Reinecke, Holger, Engelbertz, Christiane, Bauersachs, Rupert, Breithardt, Günter, Echterhoff, Hans-Herbert, Gerß, Joachim, Haeusler, Karl Georg, Hewing, Bernd, Hoyer, Joachim, Juergensmeyer, Sabine, Klingenheben, Thomas, Knapp, Guido, Christian Rump, Lars, Schmidt-Guertler, Hans, Wanner, Christoph, Kirchhof, Paulus, Goerlich, Dennis, Gerβ, Joachim, and Rump, Lars Christian

Published
2023
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11. Additional file 1 of Associations of 2D speckle tracking echocardiography-based right heart deformation parameters and invasively assessed hemodynamic measurements in patients with pulmonary hypertension

Author

Theres, Lena, Hübscher, Anne, Stangl, Karl, Dreger, Henryk, Knebel, Fabian, Brand, Anna, and Hewing, Bernd

Subjects
respiratory system, human activities
Abstract

Additional file 1: Table S1. Associations of diverse clinical characteristics and RV strain with PH; multivariate regression analysis. Table S2. Associations of diverse clinical characteristics and RA strain with PH; multivariate regression analysis.

Published
2020
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15. Treatment of Severe TRIcuspid Regurgitation in Patients with Advanced Heart Failure with CAval Vein Implantation of the Edwards Sapien XT VALve (TRICAVAL): a randomised controlled trial

Author

Dreger, Henryk, primary, Mattig, Isabel, additional, Hewing, Bernd, additional, Knebel, Fabian, additional, Lauten, Alexander, additional, Lembcke, Alexander, additional, Thoenes, Martin, additional, Roehle, Robert, additional, Stangl, Verena, additional, Landmesser, Ulf, additional, Grubitzsch, Herko, additional, Stangl, Karl, additional, and Laule, Michael, additional

Published
2020
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16. Deficiency of inactive rhomboid protein 2 (iRhom2) attenuates diet-induced hyperlipidaemia and early atherogenesis.

Author

Hannemann, Carmen, Schecker, Johannes H, Brettschneider, Alica, Grune, Jana, Rösener, Nicole, Weller, Andrea, Stangl, Verena, Fisher, Edward A, Stangl, Karl, Ludwig, Antje, and Hewing, Bernd

Subjects
ATHEROSCLEROSIS, HYPERLIPIDEMIA, WESTERN diet, ATHEROSCLEROTIC plaque, LIPOPROTEIN receptors
Abstract

Aims Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and anti-inflammatory treatment strategies are currently pursued to lower cardiovascular disease burden. Modulation of recently discovered inactive rhomboid protein 2 (iRhom2) attenuates shedding of tumour necrosis factor-alpha (TNF-α) selectively from immune cells. The present study aims at investigating the impact of iRhom2 deficiency on the development of atherosclerosis. Methods and results Low-density lipoprotein receptor (LDLR)-deficient mice with additional deficiency of iRhom2 (LDLR−/−iRhom2−/−) and control (LDLR−/−) mice were fed a Western-type diet (WD) for 8 or 20 weeks to induce early or advanced atherosclerosis. Deficiency of iRhom2 resulted in a significant decrease in the size of early atherosclerotic plaques as determined in aortic root cross-sections. LDLR−/−iRhom2−/− mice exhibited significantly lower serum levels of TNF-α and lower circulating and hepatic levels of cholesterol and triglycerides compared to LDLR−/− mice at 8 weeks of WD. Analyses of hepatic bile acid concentration and gene expression at 8 weeks of WD revealed that iRhom2 deficiency prevented WD-induced repression of hepatic bile acid synthesis in LDLR−/− mice. In contrast, at 20 weeks of WD, plaque size, plaque composition, and serum levels of TNF-α or cholesterol were not different between genotypes. Conclusion Modulation of inflammation by iRhom2 deficiency attenuated diet-induced hyperlipidaemia and early atherogenesis in LDLR−/− mice. iRhom2 deficiency did not affect diet-induced plaque burden and composition in advanced atherosclerosis in LDLR−/− mice. [ABSTRACT FROM AUTHOR]

Published
2022
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17. Monozyten und Makrophagen – Targets für eine antiinflammatorische Therapie kardiovaskulärer Erkrankungen

Author

Hewing, Bernd

Subjects
makcophages, monozytes, atherosclerosis, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
Abstract

Die Atherosklerose und die erworbene Aortenklappenstenose (AS) werden als chronisch inflammatorische Erkrankungen der arteriellen Gefäßwand bzw. des Klappengewebes angesehen. In der Pathogenese beider Erkrankungen spielen Monozyten und Makrophagen eine bedeutende Rolle und stellen daher potentielle Targets für antiinflammatorische Therapieansätze dar. Ziel einer antiinflammatorischen Therapie in der Atherosklerose ist es, die Atherogenese abzuschwächen und darüberhinaus eine Regression bereits bestehender Plaques herbeizuführen. Dazu gilt es den Gehalt an Makrophagen in atherosklerotischen Plaques zu verringern, die nachteiligen Effekte der inflammatorischen M1 Makrophagen abzuschwächen, sowie eine Verschiebung des M1/M2-Verhältnisses in Richtung des antiinflammatorischen M2 Makrophagen Phänotyps zu bewirken. Diese Ziele konnten im Mausmodell durch eine Korrektur der Hypercholesterinämie mittels Erhöhung von funktionalem Apolipoprotein A-I, sowie durch eine lokale Anwendung eines Statins im atherosklerotischen Plaque erreicht werden. Der Gehalt an Makrophagen im Gewebe wird u.a. durch die Rekrutierung von Monozyten aus dem Blut, sowie die Emigration von Makrophagen aus dem Gewebe beeinflusst. Ein genaues Verständnis dieser Prozesse ist von wesentlicher Bedeutung für die Entwicklung neuartiger Therapiekonzepte für die Atherosklerose und die AS. Es konnte gezeigt werden, dass neuronale Guidance-Moleküle (wie Netrin-1 und Semaphorin 3E) eine Retention von Makrophagen in atherosklerotischen Plaques begünstigen können. Für die AS fehlen noch grundlegende Erkenntnisse zu Monozyten-Makrophagen-Abstammungslinien um geeignete Therapieansätze entwickeln zu können. Es werden daher erstmalig Daten zur Verteilung individueller Monozyten-Subpopulationen (klassische, intermediäre und nicht- klassische Monozyten) bei der AS und nach Behandlung der AS mittels eines Aortenklappenersatzes gezeigt. Es konnte nachgewiesen werden, dass der Gehalt an intermediären Monozyten im Blut von Patienten mit hochgradiger AS erhöht ist und im Verlauf nach Beseitigung der AS mittels eines Aortenklappenersatzes abnimmt. Diese Ergebnisse dienen als Ausgangspunkt für weitere Forschungsprojekte zur Rolle der Monozyten-Subpopulationen in der Pathogenese der AS. Monozyten und Makrophagen stellen vielversprechende Targets für die antiinflammatorische Therapie kardiovaskulärer Erkrankungen dar. Die weitere Vertiefung der Erkenntnisse zur Rolle der Monozyten und Makrophagen in der Pathogenese der Atherosklerose und der AS ist notwendig, um den Weg für neuartige Ansätze zur Modulation dieser Zellen und somit für zukünftige antiinflammatorische Therapiestrategien zu bahnen., This work focuses on monocytes and macrophages as targets for anti- inflammatory therapies of cardiovascular diseases.

Published
2018
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18. Echocardiographic diagnosis, management and monitoring of pulmonary embolism with right heart thrombus in a patient with myotonic dystrophy: a case report

Author

Baumann Gert, Panda Alexander, Fallenberg Eva M, Dreger Henryk, Ghaeni Leyli, Hewing Bernd, and Borges Adrian C

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Acute pulmonary embolism (PE) is a common disease which frequently results in life-threatening right ventricular (RV) failure. High-risk PE, presenting with hypotension, shock, RV dysfunction or right heart thrombus is associated with a high mortality, particularly during the first few hours. Accordingly, it is important to commence effective therapy as soon as possible. In the case described in this report, a 49-year-old woman with myotonic dystrophy type 1 presented with acute respiratory failure and hypotension. Transthoracic echocardiography showed signs of right heart failure and a mobile right heart mass highly suspicious of a thrombus. Based on echocardiographic findings, acute thrombolysis was performed resulting in hemodynamic stabilization of the patient and complete resolution of the right heart thrombus. This case underscores the important role of transthoracic echocardiography for the diagnosis, management and monitoring of PE and underlines the efficacy and safety of thrombolysis in the treatment of PE associated with right heart thrombus.

Published
2010
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19. TCT-73 Treatment of Severe TRIcuspid Regurgitation in Patients with Advanced Heart Failure with CAval Vein Implantation of the Edwards Sapien XT VALve (TRICAVAL): a controlled prospective randomized trial

Author

Laule, Michael, primary, Mattig, Isabel, additional, Hewing, Bernd, additional, Schöbel, Christoph, additional, Knebel, Fabian, additional, Lauten, Alexander, additional, Lembcke, Alexander, additional, Thoenes, Martin, additional, Stangl, Verena, additional, Landmesser, Ulf, additional, Stangl, Karl, additional, and Dreger, Henryk, additional

Published
2018
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20. Immunoproteasome subunit ß5i/LMP7-deficiency in atherosclerosis

Author

Hewing, Bernd, primary, Ludwig, Antje, additional, Dan, Cristian, additional, Pötzsch, Max, additional, Hannemann, Carmen, additional, Petry, Andreas, additional, Lauer, Dilyara, additional, Görlach, Agnes, additional, Kaschina, Elena, additional, Müller, Dominik N., additional, Baumann, Gert, additional, Stangl, Verena, additional, Stangl, Karl, additional, and Wilck, Nicola, additional

Published
2017
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25. HDL Function, Dysfunction, and Reverse Cholesterol Transport

Author

Fisher, Edward A., Feig, Jonathan E., Hewing, Bernd, Hazen, Stanley L., and Smith, Jonathan D.

Subjects
Apolipoprotein A-I, nutritional and metabolic diseases, Biological Transport, Atherosclerosis, Article, Cholesterol, Cardiovascular Diseases, Risk Factors, Models, Animal, Disease Progression, Animals, Humans, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL
Abstract

Although high high-density lipoprotein (HDL)-cholesterol levels are associated with decreased cardiovascular risk in epidemiological studies, recent genetic and pharmacological findings have raised doubts about the beneficial effects of HDL. Raising HDL levels in animal models by infusion or overexpression of apolipoprotein A-I has shown clear vascular improvements, such as delayed atherosclerotic lesion progression and accelerated lesion regression, along with increased reverse cholesterol transport. Inflammation and other factors, such as myeloperoxidase-mediated oxidation, can impair HDL production and HDL function, with regard to its reverse cholesterol transport, antioxidant, and anti-inflammatory activities. Thus, tests of HDL function, which have not yet been developed as routine diagnostic assays, may prove useful and be a better predictor of cardiovascular risk than HDL-cholesterol levels.

Published
2012

27. Cardiac and renal function in a large cohort of amateur marathon runners

Author

Hewing, Bernd, primary, Schattke, Sebastian, additional, Spethmann, Sebastian, additional, Sanad, Wasiem, additional, Schroeckh, Sabrina, additional, Schimke, Ingolf, additional, Halleck, Fabian, additional, Peters, Harm, additional, Brechtel, Lars, additional, Lock, Jürgen, additional, Baumann, Gert, additional, Dreger, Henryk, additional, Borges, Adrian C, additional, and Knebel, Fabian, additional

Published
2015
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28. Alternatives Splicing im Intron 13 der humanen eNOS: ein potentieller Mechanismus für die Regulation der eNOS-Aktivität

Author

Hewing, Bernd

Subjects
alternative splicing, endothelium, nitric oxide, nitric oxide synthase, eNOS, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, NO
Abstract

Die endotheliale NO-Synthase (eNOS) gilt als Schlüsselenzym der vaskulären Homöostase. Neben seiner Bedeutung als potenter endogener Vasodilatator ist Stickstoffmonoxid (NO), das Produkt der eNOS, für eine Reihe gefäßprotektiver Eigenschaften verantwortlich. Während für die humane iNOS und nNOS eine Reihe von alternativen Splice-Varianten beschrieben sind, existiert bisher kein Nachweis alternativ gespleißter Isoformen für die eNOS. Im Rahmen der hier vorliegenden Arbeit konnten erstmals alternative Splice-Varianten der humanen eNOS nachgewiesen werden. Die drei neuen Splice-Varianten - eNOS13A, eNOS13B und eNOS13C - entsprechen von Exon 1 bis 13 der humanen eNOS. An das Exon 13 schließt sich jeweils ein neues Exon bestehend aus Intron 13 Sequenzen an, gefolgt von einem Poly-A-Schwanz. Im Falle einer Translation der Splice- Varianten entstehen verkürzte eNOS-Proteine, denen große Teile der Reduktase- Domäne fehlen und die keine eigene eNOS-Aktivität besitzen. Die Koexpression von eNOS mit eNOS13A in COS-7 Zellen führte zu einer Abnahme der eNOS- Aktivität durch die Bildung von Heterodimeren. Die Stabilisierung der full- length eNOS-Proteinmenge nach Proteasominhibition deutet auf einen vorzeitigen Abbau der Heterodimere über das Ubiquitin-Proteasom-System hin. Die drei eNOS Splice-Varianten werden nativ in verschiedenen Endothelzellen und in einer Vielzahl humaner Gewebe exprimiert. Eine besonders hohe Expression an eNOS13A- mRNA konnte in humanem Testis-Gewebe nachgewiesen werden. Die Ergebnisse dieser Arbeit zeigen einen neuartigen potentiellen Mechanismus zur Regulation der eNOS-Aktivität und NO-Produktion über dominant-negative Splice-Varianten der humanen eNOS., NO, the product of endothelial NOS (eNOS), is a major regulator of vascular homeostasis and a critical factor in preventing cardiovascular diseases. Whereas for human iNOS and nNOS a number of different splice variants have been described, no such splice isoforms are known for eNOS so far. This study describes three novel splice variants for human eNOS. These splice variants - termed eNOS13A, eNOS13B and eNOS13C - share the first 13 exons of human eNOS followed by novel overlapping exons containing intron 13 sequences. All three splice variants share the same polyadenylation signal followed by a poly-A tail. When translated, these splice-variants would result in truncated eNOS proteins lacking eNOS activity. Coexpression of full-length and eNOS13A in COS-7 cells diminished eNOS enzyme activity by formation of heterodimers. Coexpression in COS-7 cells with inhibition of the proteasome suggest an enhanced degradation of the heterodimers by the ubiquitin-proteasome-system. All three splice-variants were expressed in different endothelial cells and various human tissues. Expression of eNOS13A was particularly high in human testis. Taken together, these data suggest a new mechanism for the regulation of eNOS activity and NO production by dominant-negative splice variants of human eNOS.

Published
2008
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30. Effects of Native and Myeloperoxidase-Modified Apolipoprotein A-I on Reverse Cholesterol Transport and Atherosclerosis in Mice

Author

Hewing, Bernd, primary, Parathath, Saj, additional, Barrett, Tessa, additional, Chung, Wing Ki Kellie, additional, Astudillo, Yaritzy M., additional, Hamada, Tadateru, additional, Ramkhelawon, Bhama, additional, Tallant, Thomas C., additional, Yusufishaq, Mohamed Shaif S., additional, DiDonato, Joseph A., additional, Huang, Ying, additional, Buffa, Jennifer, additional, Berisha, Stela Z., additional, Smith, Jonathan D., additional, Hazen, Stanley L., additional, and Fisher, Edward A., additional

Published
2014
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32. Erratum: A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

Author

Duivenvoorden, Raphaël, primary, Tang, Jun, additional, Cormode, David P., additional, Mieszawska, Aneta J., additional, Izquierdo-Garcia, David, additional, Ozcan, Canturk, additional, Otten, Maarten J., additional, Zaidi, Neeha, additional, Lobatto, Mark E., additional, van Rijs, Sarian M., additional, Priem, Bram, additional, Kuan, Emma L., additional, Martel, Catherine, additional, Hewing, Bernd, additional, Sager, Hendrik, additional, Nahrendorf, Matthias, additional, Randolph, Gwendalyn J., additional, Stroes, Erik S. G., additional, Fuster, Valentin, additional, Fisher, Edward A., additional, Fayad, Zahi A., additional, and Mulder, Willem J. M., additional

Published
2014
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33. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

Author

Duivenvoorden, Raphaël, primary, Tang, Jun, additional, Cormode, David P., additional, Mieszawska, Aneta J., additional, Izquierdo-Garcia, David, additional, Ozcan, Canturk, additional, Otten, Maarten J., additional, Zaidi, Neeha, additional, Lobatto, Mark E., additional, van Rijs, Sarian M., additional, Priem, Bram, additional, Kuan, Emma L., additional, Martel, Catherine, additional, Hewing, Bernd, additional, Sager, Hendrik, additional, Nahrendorf, Matthias, additional, Randolph, Gwendalyn J., additional, Stroes, Erik S. G., additional, Fuster, Valentin, additional, Fisher, Edward A., additional, Fayad, Zahi A., additional, and Mulder, Willem J. M., additional

Published
2014
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35. Hypoxia Induces Netrin-1 and Unc5b in Atherosclerotic Plaques

Author

Ramkhelawon, Bhama, primary, Yang, Yuan, additional, van Gils, Janine M., additional, Hewing, Bernd, additional, Rayner, Katey J., additional, Parathath, Sajesh, additional, Guo, Liang, additional, Oldebeken, Scott, additional, Feig, Jessica L., additional, Fisher, Edward A., additional, and Moore, Kathryn J., additional

Published
2013
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36. Neuroimmune Guidance Cue Semaphorin 3E Is Expressed in Atherosclerotic Plaques and Regulates Macrophage Retention

Author

Wanschel, Amarylis, primary, Seibert, Tara, additional, Hewing, Bernd, additional, Ramkhelawon, Bhama, additional, Ray, Tathagat D., additional, van Gils, Janine M., additional, Rayner, Katey J., additional, Feig, Jonathan E., additional, O’Brien, Edward R., additional, Fisher, Edward A., additional, and Moore, Kathryn J., additional

Published
2013
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38. Abstract 19487: Simvastatin Loaded High-Density Lipoprotein Nanoparticles Reduce Inflammation in Atherosclerotic Plaques by Directly Acting on Plaque Macrophages and Inflammatory Monocytes

Author

Tang, Jun, primary, Duivenvoorden, Raphael, additional, Hewing, Bernd, additional, Izquierdo-Garcia, David, additional, Mieszawska, Aneta J, additional, van Rijs, Sarian M, additional, Cormode, David P, additional, Ozcan, Canturk, additional, Kuan, Emma L, additional, Martel, Catherine, additional, Lobatto, Mark E, additional, Stroes, Erik S, additional, Randolph, Gwendalyn J, additional, Fuster, Valentin, additional, Fisher, Edward A, additional, Fayad, Zahi A, additional, and Mulder, Willem J, additional

Published
2012
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41. Abstract 49: The Neuroimmune Guidance Molecule Semaphorin 3e Is Expressed in Macrophages of Advanced Atherosclerotic Plaques and Induces Macrophage Chemostasis

Author

Seibert, Tara, primary, Wanschel, Amarylis C, additional, Hewing, Bernd, additional, Ramkhelawon, Bhama, additional, van Gils, Janine M, additional, Rayner, Katey J, additional, Feig, Jonathan, additional, O’Brien, Edward, additional, Fisher, Edward A, additional, and Moore, Kathryn J, additional

Published
2012
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