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DGK-Logo DGK research grant: Dr. Mohammed Rabiul Hosen

January  2021 

The German Society for Cardiology (DGK) - Heart and Circulatory Research e.V. promotes the next generation of scientists in cardiology and cardiovascular basic subjects by awarding DGK research grants. 

Dr. Mohammed Rabiul Hosen, a member of the TRR259, has now received such a research grant of € 50,000 for his research project for 2021.

Dr. Hosen together with his team involved in research on cardiovascular disease (CVD), from investigating the underlying molecular mechanisms of pathogenesis in coronary heart diseases (CHDs) to the development of holistic RNA-based therapeutic approaches for the diagnosis ("Liquid Biopsies") and treatment of multifactorial CVDs. Since his PhD research at the Inst. of Cardiovascular Regeneration, Goethe University Frankfurt, he has been working on the development of RNA-based cardiovascular biomarkers/therapies by focusing on different CVDs, including atherosclerosis and its sequelae, and implementing in vitro and in vivo models (myocardial infarction, atherosclerosis, aortic valve stenosis, and heart failure).

Congratulations and good luck with your work.

Hosen_Mohammed-Rabiul2.JPG

  

Publication about an altered intercellular communication mediated by MicroRNA in chronic kidney diseases

November 02, 2020 

MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease

Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miR) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown.
The group of Andreas Zietzer et. al. could shown in this paper that EV-miR-mediated vascular intercellular communication is altered in patients with CAD and CKD, promoting CKD-induced endothelial dysfunction.

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 MicroRNA_graphical abstract_02.11.2020

 

Publication: Andreas Zietzer; Eva Steffen; Sven Niepmann; Philip Düsing; Mohammed Rabiul Hosen; Weiyi Liu; Paul Jamme; Baravan Al-Kassou; Philipp Roger Goody; Sebastian Zimmer; Katrin S Reiners; Alexander Pfeifer; Michael Böhm; Nikos Werner; Georg Nickenig; Felix Jansen

Cardiovascular Research cvaa322, 2020 Nov. 02, https://doi.org/10.1093/cvr/cvaa322

DGK-Logo Young investigator Award of the German Cardiac Society: Dr. Sven Thomas Niepmann

October 26, 2020

The "Young Investigator Awards" are presented every year at the annual conference of the German Cardiac Society (DGK). Young scientists who are not older than 35 years are honored. Several young cardiologists from the heart center of the University Hospital were honored this year also a member of the TRR259: The TRR259 member Dr. Sven Thomas Niepmann was awarded with the first prize (1.500€) for his work: “Cyclodextrin reduces aortic valve stenosis development in mice”

Link to the DGK-Website

Niepmann_Sven

 

Publication about pulmonary hypertension associated with left-sided heart failure

 September 21, 2020

Pulmonary hypertension associated with left-sided heart failure

Pulmonary hypertension is a common phenomenon in heart failure patients that is highly relevant for morbidity and outcome. Although postcapillary in nature, the pathophysiology of pulmonary hypertension in patients with heart failure with reduced or preserved ejection fraction is complex, and decisions about management strategies remain challenging.

Recently, the hemodynamic definitions and subclassification of postcapillary pulmonary hypertension have been revisited. The distinction between isolated postcapillary pulmonary hypertension (IpcPH) and combined post and precapillary pulmonary hypertension (CpcPH) and their definition are essential. Novel data on the prognostic impact of hemodynamic variables and right ventricular function highlight the importance of cardiopulmonary interaction in patients with left-sided heart failure (LHF). Furthermore, the impact of management strategies including medical therapy, remote hemodynamic monitoring, and interventional approaches on hemodynamics and outcome has recently been investigated. Here, the group of Joana Adler et. al critically review recent developments and future considerations in this field, and highlight distinct treatment strategies targeting the underlying left heart condition, the pulmonary circulation, and/or impaired right ventricular function.

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Publication: Adler J, Gerhardt F, Wissmüller M, Adler C, Baldus S, Rosenkranz S. Pulmonary hypertension associated with left-sided heart failure. Curr Opin Cardiol. 2020 Sep 21. doi: 10.1097/HCO.0000000000000791. Epub ahead of print. PMID: 32969856

  

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Open PhD-postion

The Institute of Physiology I invites applications for a PhD position - Endothelial disease mechanisms

You can find more information here

Publication about Nitro-fatty acids and their influence in ischemic ventricular arrhythmias

September 18, 2020

Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. The group of Martin Mollenhauer et. al demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.

 

Nitro-fatty acids

 

 NO2-OA prevents acute ischemia induced ventricular tachycardias.

 

Publication: Mollenhauer M, Mehrkens D, Klinke A, Lange M, Remane L, Friedrichs K, Braumann S, Geißen S, Simsekyilmaz S, Nettersheim FS, Lee S, Peinkofer G, Geisler AC, Geis B, Schwoerer AP, Carrier L, Freeman BA, Dewenter M, Luo X, El-Armouche A, Wagner M, Adam M, Baldus S, Rudolph V.

Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis. Sci Rep. 2020 Sep 18;10(1):15319. doi: 10.1038/s41598-020-71870-6. PMID: 32948795.

 

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Publication about hnRNPU and its function 

July 02, 2020

The RNA-binding protein hnRNPU regulates the sorting of microRNA-30c-5p into large extracellular vesicles

The transfer of microRNAs (miRs) via extracellular vesicles (EVs) is a functionally relevant mechanism of intercellular communication that regulates both organ homoeostasis and disease development. Little is known about the packaging of miRs into EVs. Previous studies have shown that certain miRs are exported by RNA-binding proteins into small EVs, while for other miRs and for large EVs, in general, the export mechanisms remain unclear. Therefore, a proteomic analysis of endothelial cell-derived large EVs was performed, which revealed that heterogeneous nuclear ribonucleoprotein U (hnRNPU) is abundantly present in EVs. The specific role of hnRNPU for vesicular miR-sorting was confirmed independently by gain- and loss-of-function experiments.

In summary the group of Felix Jansen (AG Jansen), Zietzer and Hosen et. al. could show that hnRNPU retains miR-30c-5p and other miRs and thereby prevents their export into large EVs. The data presented provide a novel and functionally relevant mechanism of vesicular miR export.

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Andreas_Zietzer_hnRNPU_Bild

 

 Graphical summary of the study results (https://www.tandfonline.com/doi/full/10.1080/20013078.2020.1786967)

 

Publication: Andreas Zietzer, Mohammed Rabiul Hosen, Han Wang, Philip Roger Goody, Marc Sylvester, Eicke Latz, Georg Nickenig, Nikos Werner & Felix Jansen

  

The RNA-binding protein hnRNPU regulates the sorting of microRNA-30c-5p into large extracellular vesicles; Journal of Extracellular Vesicles 2020 Jul 02, 9:1, 1786967, DOI: 10.1080/20013078.2020.1786967

 

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Publication: Receptor makes mice strong and slim

June 25, 2020

Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity

Increasing abdominal girth and shrinking muscles are two common side effects of aging. Researchers at the University of Bonn have discovered a receptor in mice that regulates both effects. Experiments with human cell cultures suggest that the corresponding signaling pathways might also exist in humans. The study, which also involved researchers from Spain, Finland, Belgium, Denmark and the USA, has now been published in the renowned journal "Cell Metabolism"

 

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the A2B receptors_A.Pfeifer

Publication: Thorsten Gnad, Gemma Navarro, Minna Lahesmaa, Laia Reverte-Salisa, Francesca Copperi, Arnau Cordomi, Jennifer Naumann, Aileen Hochhäuser, Saskia Haufs-Brusberg, Daniela Wenzel, Frank Suhr, Naja Zenius Jespersen, Camilla Scheele, Volodymyr Tsvilovskyy, Christian Brinkmann, Joern Rittweger, Christian Dani, Mathias Kranz, Winnie Deuther-Conrad, Holger K. Eltzschig, Tarja Niemi, Markku Taittonen, Peter Brust, Pirjo Nuutila, Leonardo Pardo, Bernd K. Fleischmann, Matthias Blüher, Rafael Franco, Wilhelm Bloch, Kirsi A. Virtanen, Alexander Pfeifer

Adenosine/A2B receptor signaling ameliorates the effects of ageing and counteracts obesity. Cell Metabolism, DOI: https://doi.org/10.1016/j.cmet.2020.06.006 

 

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Publication about MicroRNAs as master regulators of Atherosclerosis

June 8, 2020

MicroRNAs As Master Regulators of Atherosclerosis: From Pathogenesis to Novel Therapeutic Options

The Department of Internal Medicine II from the University Bonn published a new paper about microRNAs (miRNAs) as master regulators of atherosclerosis. Cardiovascular disease remains the major cause of morbidity and mortality worldwide. There are indications that atherosclerosis and its sequelae, coronary artery disease, contribute to the majority of cardiovascular death. It was shown that small RNAs, especially micro RNAs (miRNAs) are dynamic regulators of disease pathogenesis. They are considered to be central during the regulation of gene expression through numerous mechanisms and provide a means to develop biomarkers and therapeutic tools for the diagnosis and therapy of atherosclerosis. MiRNAs represent a valuable tool for diagnosing and monitoring of cardiovascular disease.
This paper will give an overview of the current developmental progression of RNA therapeutics as a holistic approach for treating cardiovascular diseases in different animal models and clinical trials. Future interrogations are warranted for the development of miRNA-based therapeutics to overcome challenges for the treatment of the disease
 

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Publication: Mohammed Rabiul Hosen, Philip Roger Goody, Andreas Zietzer, Georg Nickenig, and Felix Jansen

MicroRNAs As Master Regulators of Atherosclerosis: From Pathogenesis to Novel Therapeutic Options; Antioxidants & Redox Signaling; 8 Jun 2020; https://doi.org/10.1089/ars.2020.8107

 

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ARS_Coverletter

Copyright 2020, Mary Ann Liebert, Inc., publishers 

 

Publication about Hot spot 19F magnetic resonance imaging of inflammation 

May 07, 2020

Hot spot 19FHot spot 19F magnetic resonance imaging of inflammation

 

Among the preclinical molecular imaging approaches, lately fluorine (19F) magnetic resonance imaging (MRI) has garnered significant scientific interest in the biomedical research community, due to the unique properties of fluorinated materials and the 19F nucleus. Fluorine is an intrinsically sensitive nucleus for MRI—there is negligible endogenous 19F in the body and, thus, no background signal which allows the detection of fluorinated materials as “hot spots” by combined 1H/19F MRI and renders fluorine‐containing molecules as ideal tracers with high specificity. In addition, perfluorocarbons are a family of compounds that exhibit a very high fluorine payload and are biochemically as well as physiologically inert. Perfluorocarbon nanoemulsions (PFCs) are well known to be readily taken up by immunocompetent cells, which can be exploited for the unequivocal identification of inflammatory foci by tracking the recruitment of PFC‐loaded immune cells to affected tissues using 1H/19F MRI. The required 19F labeling of immune cells can be accomplished either ex vivo by PFC incubation of isolated endogenous immune cells followed by their re‐injection or by intravenous application of PFCs for in situ uptake by circulating immune cells. With both approaches, inflamed tissues can unambiguously be detected via background‐free 19F signals due to trafficking of PFC‐loaded immune cells to affected organs. To extend 19F MRI tracking beyond cells with phagocytic properties, the PFC surface can further be equipped with distinct ligands to generate specificity against epitopes and/or types of immune cells independent of phagocytosis. Recent developments also allow for concurrent detection of different PFCs with distinct spectral signatures allowing the simultaneous visualization of several targets, such as various immune cell subtypes labeled with these PFCs. Since ligands and targets can easily be adapted to a variety of problems, this approach provides a general and versatile platform for inflammation imaging which will strongly extend the frontiers of molecular MRI.

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Picture: Labelling approaches for 19F MRI (https://onlinelibrary.wiley.com/doi/full/10.1002/wnan.1639)

Publication: Pascal Bouvain, Sebastian Temme, Ulrich Flögel

Hot spot 19F magnetic resonance imaging of inflammation; Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020 May 07;e1639. doi:10.1002/wnan.1639

 

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Publication about Thymic stromal lymphopoietin in atherogenesis 

April 13, 2020 

Thymic stromal lymphopoietin is a key cytokine for the immunomodulation of atherogenesis with Freund's adjuvant

Adaptive immune responses regulate the development of atherosclerosis, with a detrimental effect of type 1 but a protective role of type 2 immune responses. Immunization of Apolipoprotein E-deficient (ApoE−/−) mice with Freund's adjuvant inhibits the development of atherosclerosis. However, the underlying mechanisms are not fully understood.
Thymic stromal lymphopoietin (TSLP) is an IL7-like cytokine with essential impact on type 2 immune responses (Th2). Thymic stromal lymphopoietin is strongly expressed in epithelial cells of the skin, but also in various immune cells following appropriate stimulation.
The group of Martin Steinmetz investigated whether TSLP may be crucial for the anti-atherogenic effect of Freund's adjuvant. They found that subcutaneous injection of complete Freund's adjuvant (CFA) rapidly led to the expression of TSLP and IL1β at the site of injection. 

 

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Publication: Martin Steinmetz, Ludivine Laurans, Sarah Nordsiek, Lena Weiß, Bieke van der Veken, Padmapriya Ponnuswamy, Bruno Esposito, Marie Vandestienne, Andreas Giraud, Cristina Göbbel, Eva Steffen, Tobias Radecke, Stephane Potteaux, Georg Nickenig, Tienush Rassaf, Alain Tedgui, Ziad Mallat; 

Thymic stromal lymphopoietin is a key cytokine for the immunomodulation of atherogenesis with Freund's adjuvant; 

Journal of Cellular and Molecular Medicine 2020;00:1–9; DOI: 10.1111/jcmm.15235

 

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TRR259 Retreat November 11-12, 2020

November 11-12, 2020 in the Biomedical Center Bonn

Location

Biomedical Center Bonn                               
Venusberg-Campus 2
53127 Bonn

BMZ

(c) https://www.schloss-rheinfels.de/bildergalerie/

 

Fuji Visualsonic Seminar April 2, 2020

 April 2, 2020 in Bonn, University Hospital Bonn 

Join the Photoacoustic Imaging Workshop with the Vevo3000 from Fuji Visualsonic. Learn how the system works and track changes in myocardial oxygen saturation in real-time.

 

When? April 2, 2020 during the morning

Where? via live stream (please contac Marta Stei: marta.stei(at)ukbonn.de)

VEVO3000 Seminar

(c) https://www.visualsonics.com/product/imaging-systems/vevo-lazr-x

More information: https://www.visualsonics.com/event/workshops/photoacoustic-imaging-workshop-vevo-lazr-x

Publication about Aortic Valve Stenosis in ATVB  

March 12, 2020 

Aortic Valve Stenosis – From Basic Mechanisms to Novel Therapeutic Targets

Aortic valve stenosis (AVS) is the most common acquired heart valve disease in the western world. The morbidity and mortality associated with AVS is tremendous and the 2-year mortality rate is around 50%. A complex process of endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation and subsequently calcification leads to remodeling and thickening of the aortic valve cups. The changes results in valve obstruction. The underlying pathophysiology of calcification are still unclear and no pharmacotherapy has been established to prevent aortic valve calcification. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.

 

Publication: Philip Roger Goody, Mohammed Rabiul Hosen, Dominik Christmann, Sven Thomas Niepmann, Andreas Zietzer, Matti Adam, Florian Bönner, Sebastian Zimmer, Georg Nickenig, Felix Jansen: Aortic Valve Stenosis – From Basic Mechanisms to Novel Therapeutic Targets; Arteriosclerosis, Thrombosis, and Vascular Biology 2020;40:885–900; DOI: 10.1161/ATVBAHA.119.313067

Cover ATVB

© 2020 American Heart Association, Inc.

 

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1st International Symposium March 12, 2020

March 12, 2020 in Bonn

Speaker
Prof. Bert Callewaert, University of Ghent
PD Dr. Jennifer Eßer, University of Freiburg
Prof. Stefan Offermanns, Max Planck Institute, Bad Nauheim
Prof. Hiroki Kato, University of Bonn
Dr. Christine Quast, University of Düsseldorf
PD Dr. Sebastian Zimmer, University of Bonn 
Prof. Gerhard Sengle, University of Cologne

Date and Time
March 12, 2020
12:30 - 5 pm

 

Location 
Lecture Hall, teaching building (no. 10) 
University Hospital Bonn
Venusberg-Campus 1

International-Symposium_Poster

(c) Giacomo Zucca/Bundesstadt Bonn

 

1st IS_Bilder_Einleitung

(c) Marika Enders, Simon Görgen, Giacomo Zucca/Bundesstadt Bonn

 

 More information and pictures

Kick-Off-Meeting St. Goar November 8-10, 2019

November 8 – 9, 2020

Loreleyblick_1

The TRR259 starts with the yearly Kick-Off-Meeting to familiarize the new members of the integrated research group members and to facilitate their entry into the TRR259.


The Kick-Off-Meeting took place at the Schloss Rheinfels in St. Goar from November 8-10, 2019.

The program of the event included lectures from every project of the TRR259 a meeting of the iRTG-members and a hiking tour to the Loreleyblick.

 

For more information and pictures of the event click here.

(c) Marika Enders 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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