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Essen, 01.10.2018

Interview with Prof. Dobrev at 57th National Congress of Romanian Society of Cardiology, September 19-22, Romania.

Prof. Dobrev was invited to participate at the 57th National Congress of Romanian Society of Cardiology, September 19-22, Romania, as a distinguished lecturer delivering a keynote lecture with the title “Antiarrhythmic drug therapy for atrial fibrillation in the next 10 years”. See also the related interview with Prof. Dobrev about the future of atrial fibrillation therapy (the link to the interview can be found here). In addition, in recognition of his important contributions to improving our understanding of the mechanisms and therapy of atrial fibrillation, Prof. Dobrev was awarded the prestigious title of Honorary Member of Romanian Society of Cardiology.


Essen, 15.06.2018

Institute of Pharmacology hosts the 42th Annual Meeting of the European Society of Cardiology Working Group on Cardiac Cellular Electrophysiology.

This year (June 15-17) the Institute of Pharmacology hosted the 42th Annual Meeting of the European Society of Cardiology Working Group on Cardiac Cellular Electrophysiology (EWGCCE), which was organized by Prof. Dr. med. Dobromir Dobrev (Chair of EWGCCE) and his team. Approximately 150 scientists from different European countries traveled to Essen to exchange the latest results and ideas in experimental and translational research on ion channel function and dysfunction and arrhythmia mechanisms. More than 90 keynote lectures, oral and poster presentations were deliver during the meeting by international experts and young scientists in an incredible friendly and stimulating spirit. The Carmeliet-Coraboeuf-Weidmann Keynote Lecture 2018 was given by Prof. Karin Sipido from Leuven, Belgium, entitled "Anti-arrhythmic targets in ischemic cardiomyopathy".


Essen, 07.05.2018

Ms. Marina Schäfer successfully completed her dissertation.

The Institute of Pharmacology congratulates Ms. Marina Schäfer on her PhD and wish her all the best for the future.


Essen, 06.04.2018

Nachruf für Prof. Dr. med. Karl H. Jakobs

Am 06. April 2018 verstarb Prof. Dr. med. Karl H. Jakobs, ehemaliger Direktor des Institutes für Pharmakologie, unerwartet im Alter von 76 Jahren an seinem Wohnort in Heidelberg. Karl H. Jakobs wurde am 04. November 1941 in Rissenthal im Saarland geboren. Nach dem Abitur an der Internatsschule der Steyler Mission in Mosbach, Baden, im Jahr 1961 nahm er ein Studium der Theologie und Philosophie an der Universität Wien auf, an der er 1964 das Philosophikum ablegte. Er wechselte dann 1965 an die Universität Heidelberg, an der er sich für Humanmedizin einschrieb. Schon während des Studiums folgte er seiner Neigung für die Wissenschaft und begann eine Promotion am Pharmakologischen Institut der Universität Heidelberg in der Arbeitsgruppe von Günter Schultz. Nach Staatsexamen und Approbation, promovierte er 1971 mit einer Arbeit über die Regulation von cAMP in der Rattenniere und schloss sich dem Pharmakologischen Institut als wiss. Mitarbeiter an. 1979 habilitierte er sich für das Fach Pharmakologie und Toxikologie und wurde 1982 zum außerplanmäßigen Professor ernannt. Nach dem er 1983 einen Ruf auf eine Professur der Universität Bonn abgelehnt hatte, wurde er 1984 Nachfolger von Günter Schultz als außerordentlicher Professor am Pharmakologischen Institut der Universität Heidelberg. Im April des Jahres 1991 folgte er einem Ruf der damaligen Universität-Gesamthochschule Essen auf den Lehrstuhl für Pharmakologie und leitete das Institut für Pharmakologie der Medizinischen Fakultät bis zu seiner Pensionierung am 31. Juli 2007. Seit 1992 war er zudem Mitglied der Ethikkommission, die er seit 1998 auch leitete. Auch nach seiner Pensionierung begleitete er dieses Amt bis ins Jahr 2010 weiter, zog sich dann aber ins Privatleben zurück. Wissenschaftlich beschäftigte sich Karl H. Jakobs sehr erfolgreich mit molekularen Mechanismen der zellulären Signaltransduktion durch G-Protein-gekoppelte Rezeptoren und deren zellulären Effektoren. Insgesamt sind mehr als 260 wissenschaftliche Arbeiten mit ihm als Autor erschienen. Zu seinen wichtigsten Beiträgen zählen die Entdeckung der inhibitorischen Regulation der Adenylylzyklase und die Erkenntnis, dass auch die -Untereinheiten heterotrimerer G-Proteine aktiv an der Signaltransduktion beteiligt sind. Während seiner Zeit in Essen entwickelte er mit seinen Mitarbeitern neue Methoden zur Aktivitätsbestimmung heterotrimerer G-Proteine und identifizierte neue Signalwege zur Regulation wichtiger zellulärer Signalüberträger wie die Phospholipasen C bzw. D und Sphingosinkinasen. Seine Forschung wurde dabei kontinuierlich durch die Deutsche Forschungsgemeinschaft gefördert. Da er die Pharmakologie als ein Bestandteil der Medizin verstand, besaß die Zusammenarbeit in Forschung und Lehre mit klinischen Kollegen einen hohen Stellenwert. In seiner Arbeitsgruppe in Heidelberg und seinem Institut in Essen gab er deswegen zahlreichen Klinikern die Möglichkeit zum experimentellen Arbeiten. Mit Karl H. Jakobs verliert die Medizinische Fakultät der Universität Duisburg-Essen einen angesehen Wissenschaftler und engagierten akademischen Lehrer. Wir werden dem Verstorbenen ein ehrendes Andenken bewahren.

Für das Institut für Pharmakologie:
Prof. Dr. Dobromir Dobrev
Universitätsklinikum Essen
Hufelandstr. 55
45122 Essen
Pharmakologie-Sekretariat@uk-essen.de

Für die ehemaligen Mitarbeiter:
Prof. Dr. Thomas Wieland
Experimentelle Pharmakologie Mannheim
Ludolf-Krehl-Str. 13-17
68167 Mannheim
epm@medma.uni-heidelberg.de



Essen, 20.12.2017

Merry Christmas from the Institute of Pharmacology

The Institute of Pharmacology wishes everyone a happy holiday season, merry Christmas, and all the best for 2018!



Essen, 25.09.2017

Mrs. Azinwi Phina Muna successfully completed her dissertation.

The Institute of Pharmacology congratulates Mrs. Azinwi Phina Muna on her PhD and wish her all the best for the future.

Essen, 19.07.2017

Mrs. Pegah Erfanian-Trudrung successfully completed her dissertation.

The Institute of Pharmacology congratulates Mrs. Pegah Erfanian-Trudrung on her PhD and wish her all the best for the future.


Essen, 03.07.2017

Tina Veleva won Poster Award at the EWGCCE meeting 2017 in Vienna, AT.

Tina Veleva has been selected for the Poster Award at the annual meeting of European Society of Cardiology Working Group on Cardiac Cellular Electrophysiology (EWGCCE) for her poster presentation “The role of the inflammasome in atrial fibrillation”. The 41th Annual Meeting of the EWGCCE was hold in conjunction with the EHRA EUROPACE -CARDIOSTIM 2017 congress in June in Vienna and brought together many fields of basic and clinical research.


Essen, 02.05.2017

Prof. Dobromir Dobrev has been awarded a RO1 grant from the National Institutes of Health, USA

Inflammation has been frequently associated with atrial fibrillation, the most common clinical arrhythmia. However, the causative role and the underlying mechanisms of inflammation-associated atrial fibrillation remain poorly understood. Prof. Dobromir Dobrev and Dr. Na Li (Baylor College of Medicine, Houston, USA) have been awarded a prestigious RO1 grant from the National Institutes of Health, USA (title: The Role of Inflammasome in the Pathogenesis of Atrial Fibrillation, Proposal No. RO1 HL136389-01, funding duration 2017-2021). The grant will comprehensively investigate the role of a specific component of inflammation, the NLRP3 inflammasome, in the pathophysiology of atrial fibrillation. It is hoped that this research will lead to the identification of novel drug targets which might foster the development of new therapeutics with improved efficacy and safety profiles.


Essen, 24.04.2017

Marina Schäfer and Azinwi Phina Khan receive Travel Awards for the 83. Annual Spring Meeting of the German Society of Cardiology 2017

Marina Schäfer and Azinwi Phina Khan were awarded with Travel Grants to present their posters entitled “Rezeptor-unabhängige NDPK-B und NDPK-C vermittelte Signalübertragung über Gs-Proteine bei experimentellem und klinischem Vorhofflimmern” and "Cellular mechanisms underlying post-operative atrial fibrillation in patients". The 83. Annual Spring Meeting of German Society of Cardiology (DGK) is the biggest clinical society in Europe and brings many fields of basic and clinical research together.


Essen, 20.02.2017

Open Postdoc position

The Institute of pharmacology offers an open postdoctoral position. For more informations see here


Essen, 01.02.2017

DZHK-Paper of the month

The group of Prof. Dobrev, director of the Institute of Pharmacology, in a close collaboration with the group of Prof. Thomas Wieland from the University of Heidelberg (Medical Faculty Mannheim) published a study in Circulation (Abu-Taha et al., Circulation 2016; published online on Dec 7) showing for the first time enhanced nucleoside diphosphate kinases contribute significantly to the detrimental decrease in cAMP and related PKA signaling typifying patients with chronic heart failure. This manuscript was selected by the German Cardiovascular Centre (DZHK) as the "DZHK-Paper of the month" (see here)

Abu-Taha IH*, Heijman J*, Hippe HJ, Wolf NM, El-Armouche A, Nikolaev VO, Schäfer M, Würtz CM, Neef S, Voigt N, Baczkó I, Varró A, Müller M, Meder B, Katus HA, Spiger K, Vettel C, Lehmann LH, Backs J, Skolnik EY, Lutz S, Dobrev D#, Wieland T# (2017) Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure. Circulation, published online on December 07, 2016 (doi: https://doi.org/10.1161/CIRCULATIONAHA.116.022852). *equally contributing first authors; #equally contributing co-senior and co-correspondence authors.

Essen, 22.12.2016

Merry Christmas from the Institute of Pharmacology

The Institute of Pharmacology wishes everyone a happy holiday season, merry Christmas, and all the best for 2017!



Essen, 08.12.2016

Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure

Heart failure (HF) remains a common cause of death and disability and is associated with altered signal transduction via β-adrenoceptors and G proteins, resulting in reduced adenylyl cyclase-mediated cAMP formation and contributing to contractile dysfunction. Nucleoside diphosphate kinases (NDPKs) can modulate G-protein activity and are enriched at the plasma membrane of end-stage HF patients. However, their relevance for HF pathophysiology is largely unknown, particularly for the NDPK-C isoform.

Members of the Institute of Pharmacology, together with collaborators from various other centers in Germany and abroad, published a study in the most recent edition of Circulation, showing for the first time a potential critical role for NDPK-C in the suppression of cAMP formation in HF patients. In particular, this study identified that NDPK-C is crucial for the interaction between NDPKs and G proteins, building complexes and scaffolding them at the plasma membrane. These interactions regulate cAMP levels and cardiomyocyte contractility. In HF patients, NDPK-C switched from predominantly Gs stimulation to activation of Gi. Our findings provide a potential mechanism for the detrimental decrease in cAMP and related dysfunction previously described in HF patients, and position NDPK-C as a novel critical determinant of βAR/cAMP signaling that contributes to impaired cardiac function and remodeling in human HF.

Reference: Abu-Taha IH*, Heijman J*, Hippe HJ, Wolf NM, El-Armouche A, Nikolaev VO, Schäfer M, Würtz CM, Neef S, Voigt N, Baczkó I, Varró A, Müller M, Meder B, Katus HA, Spiger K, Vettel C, Lehmann LH, Backs J, Skolnik EY, Lutz S, Dobrev D#, Wieland T# (2016) Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure. Circulation, Published online on Dec 7, 2016. *equally contributing first authors, #co-senior and co-correspondence authors


Essen, 26.10.2016

ExpertScape ranks Prof. Dobrev and Prof. Nattel as worldwide leading experts on Atrial Fibrillation

Prof. Dobromir Dobrev and Prof. Stanley Nattel (Adjunct Professor in Institute of Pharmacology) have been named by the health information website, ExpertScape.com, as world experts on Atrial Fibrillation (Prof. Nattel ranks #3, Prof. Dobrev ranks #22 among all leading experts, only top 60 worldwide experts shown) in a ranking of experts for the understanding, diagnostic, and treatment of this disease. For their expertise in Heart the website ranks Prof. Nattel as worldwide leader (#1) and Prof. Dobrev as rank #9. ExpertScape produces its rankings through objectively analyzing data gathered via PubMed. Professor Dobrev’s and Nattel’s positions are based on more than 100 articles published between 2006 and 2015.

A printed list can be found here (4 pages).


Essen, 05.09.2016

Dr. Shokoufeh Ghezelbash won Poster Award at the EWGCCE meeting 2016 in Glasgow, GB.

Dr. Ghezelbash has been selected for the Poster Award at the annual meeting of European Society of Cardiology Working Group on Cardiac Cellular Electrophysiology (EWGCCE) for her poster presentation “Enhanced Expression and PKCδ-mediated Hyperphosphorylation underlie the Proarrythmic Increase in NCX1 Activity in Patients with Chronic Atrial Fibrillation”. The 40th Annual Meeting of the EWGCCE was hold this year in Glasgow and covered many relevant topics of basic cardiac electrophysiology

Essen, 05.09.2016

Dr. Cristina E. Molina received Travel Award to attend the EWGCCE meeting 2016 in Glasgow, GB.

Dr. Molina has been distinguished with a Travel Grant to attend the annual meeting of European Society of Cardiology Working Group on Cardiac Cellular Electrophysiology (EWGCCE) presenting her work entitled “PDE8 is an novel regulator of cAMP signaling in human atrial fibrillation”.The 40th Annual Meeting of EWGCCE was hold this year in Glasgow and covered many relevant topics of basic cardiac electrophysiology.

Essen, 11.07.2016

Prof Dobromir Dobrev interviewed by Scientists of Tomorrow from the European Society of Cardiology

A link to the interview can be found here


Essen, 25.05.2016

Prof. Fritz Sörgel organizes 2nd Doping Congress in Frankfurt/Main


Mannheim, 30.03.2016

PD Dr. Niels Voigt elected as vice chair of the Working Group of Cellular Electrophysiology (AG18) of the German Cardiac Society

During the annual scientific meeting of the German Cardiac Society PD Dr. Niels Voigt was elected as vice chair of the Working Group of Cellular Electrophysiology (AG18). Dr. Voigt takes over Prof. Dr. Dierk Thomas's position, who will be the chair of the working group. The aim of the working group is to develop a more profound understanding of the electrophysiological regulation of different cardiac cells from healthy and diseased hearts and thus allow the development of new mechanism-based therapeutic strategies. A link to the website of the Working Group can be found here.


Essen, 30.03.2016

Pegah Erfanian-Abdoust receives Travel Award for the 82. Annual Spring Meeting of the German Society of Cardiology 2016

Pegah Erfanian-Abdoust has been awarded with a Travel Grant to present her poster entitled “A new computational model for the SERCA2a-regulation by phospholamban and sarcolipin in human atrial cardiomyocytes”. The 82. Annual Spring Meeting of German Society of Cardiology (DGK) is the biggest clinical society in Europe and brings many fields of basic and clinical research together.



Essen, 01.02.2016

Prof. Dr. rer. nat. Erich Wettwer joins the Institute of Pharmacology as a consultant in cardiac electrophysiology.


Essen, 18.12.2015

Teaching Award 2015 for PD Dr. Niels Voigt

On December 18th, 2015, on the occasion of this years "exam celebrations", PD Dr. Niels Voigt has been awarded with the "Teaching Award of the Medical Faculty of the University Duisburg-Essen". For Dr. Voigt this award is particularly important since the students themselves are nominating the awardees during the evaluation process (“EVALUNA”). The price further encourages Dr. Voigt’s enthusiasm in training and teaching of medical students.

A link to the website of the Medical Faculty of the University Duisburg-Essen can be found here.


Essen, 26.10.2015

Honorary Symposium of the 100th anniversary of Paul Ehrlich’s death

The institute of Pharmacology organized a Symposium to honor the 100th Anniversary of Paul Ehrlich’s death. Paul Ehrlich was a german physician and scientist who worked in the fields of hematology, immunology, antimicrobial chemotherapy, and pharmacology, receiving the Nobel Prize in Physiology or Medicine for his contributions to immunology in 1908. Opening talks were given by the Dean of the Faculty of Medicine, Professor Buer and Professor Dobrev (Director of the Institute of Pharmacology). Professor Sörgel from the Institute of Biomedical and Pharmaceutical Research, Nürnberg, Germany gave an excellent overview about Paul Ehrlich’s life and work. The keynote lecture about „Therapy of Nosocomial Pneumonia“ was given by Professor Drusano from the University of Florida, USA.

Photo, from left to the right: Professor J. Buer, Professor D. Dobrev, Professor G. L. Drusano, and Professor F. Sörgel.



Essen, 27.08.2015

Summer Barbecue Party of the Institute of Pharmacology

The members of the Institute of Pharmacology enjoyed a socializing summer day in the "Gruga Park" having a barbecue.



Essen, 17.08.2015

Prof. Dobrev appointed Adjunct Professor at Baylor College of Medicine, Houston, USA


Essen, 07.08.2015

Prof. Dr. Fritz Sörgel interviewed about overall condemnation of athleitics organisations


Essen, 03.08.2015

Prof. Dr. Fritz Sörgel interviewed about athletes and doping


Essen, 20.07.2015

Prof. Stanley Nattel as Adjunct Professor at Institute of Pharmacology


Essen, 15.07.2015

Netherlands Organisation for Scientific Research (NWO) ‘Veni’ grant for Dr. Jordi Heijman


Essen, 04.07.2015

Prof. Dr. Fritz Sörgel interviewed about tour de france and doping


Essen, 29.05.2015

DZHK-Paper of the month

The group of Prof. Dobrev, director of the Institute of Pharmacology, in a close collaboration with the group of Prof. Dierk Thomas from the University of Heidelberg published a study in Circulation (Schmidt et al., Circulation 2015; published online on May 7) showing for the first time that two-pore K+ channels contribute significantly to the proarrhythmic shortening of atrial action potential in patients with chronic atrial fibrillation. This manuscript was selected by the German Cardiovascular Centre (DZHK) as the "DZHK-Paper of the month" (see http://dzhk.de/paper-of-the-month/).

 

Reference:

Schmidt C, Wiedmann F, Voigt N, Zhou XB, Heijman J, Lang S, Albert V, Kallenberger S, Ruhparwar A, Szabó G, Kallenbach K, Karck M, Borggrefe M, Biliczki P, Ehrlich JR, Baczkó I, Lugenbiel P, Schweizer PA, Donner BC, Katus HA, Dobrev D*, Thomas D* (2015) Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation. Circulation, 132:82-92. *equally contributed senior authors.

 


Essen, 06.05.2015

Dr. Shokoufeh Ghezelbash receives Travel Award for EHRA EUROPACE - CARDIOSTIM 2015

Dr. Ghezelbash has been distinguished with a Travel Grant from the scientific committee of European Working Group on Cardiac Cellular Electrophysiology (EWGCCE) to present her work entitled “Determinants of Altered Atrial Na+-Ca2+ Exchanger Function in Chronic Atrial Fibrillation”. The 39th Annual Meeting of EWGCCE is hold this year in conjunction with the EHRA EUROPACE -CARDIOSTIM 2015 congress in June in Milan and will bring together many fields of basic and clinical research.



Essen, 23.04.2015

Ilona Maria Schirmer receives Travel Award for HRS 2015

Ilona Maria Schirmer was awarded with a Travel Grant from the “German Academic Exchange Service (DAAD)” to present her study “Altered Composition of the Ryanodine Receptor Channel Complex in Patients with Chronic Atrial Fibrillation” at the Annual Meeting of the Heart Rhythm Society 2015 in Boston, USA. The HRS congress is the worldwide most important international meeting for cardiac arrhythmias integrating the many fields of basic and clinical research including disease management.



Essen, 01.04.2015

Pegah Erfanian-Abdoust receives Travel Award for the 81.Annual Spring Meeting of the German Society of Cardiology 2015

Pegah Erfanian-Abdoust has been awarded with a Travel Grant to present her poster entitled “Modelling the SERCA2a regulation by phospholamban and sarcolipin in the heart”. The 81th Annual Spring Meeting of German Society of Cardiology (DGK) is the biggest clinical society in Europe and brings many fields of basic and clinical research together.



Essen, 13.04.2015

Oskar Lapp Research Award

On April 9th, 2015, during the opening ceremony of the 81st annual scientific sessions of the German Cardiac Society, PD Dr. med. Niels Voigt and Dr. Jordi Heijman were awarded the Oskar Lapp Research Award for their joint publication “Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation” published in Circulation. Both Mrs. Lapp and her son were present during the award ceremony.



Essen, 03.03.2015

Prof. Dr. Fritz Sörgel interviewed about soccer and doping


Essen, 18.01.2015

Inaugural Lecture Priv.-Doz. Dr. med. Niels Voigt

On January 16, 2015 at 15:00h, PD Dr. med. Niels Voigt gave his inaugural lecture: 'Mord aus zarter Hand – Berühmte Giftmorde aus Sicht eines Pharmakologen' as part of the completion of his habilitation. Dr. Voigt spoke about three famous cases of poisoning known from popular literature and analyzed them from the point of view of a pharmacologist. The lecture-hall (Deichmann-Auditorium) was almost fully occupied.



Essen, 15.01.2015

Drs. Voigt and Heijman win the 2015 Oskar Lapp Research Award of the German Cardiac Society

Priv.-Doz. Dr. med. Niels Voigt and Dr. Jordi Heijman of the Institute of Pharmacology have been awarded the Oskar Lapp Research Award (Oskar-Lapp-Forschungspreis) 2015 of the German Cardiac Society (Deutsche Gesellschaft für Kardiologie, DGK) for their joint publication ‘Cellular and Molecular Mechanims of Atrial Arrhythmogenesis in Patients with Paroxysmal Atrial Fibrillation’ (Circulation 2014. 129: 145-156). The Oskar Lapp Research Award is an important award for scientists <35 years. It is the first award of the DGK without thematic restrictions. Its intention is to expand the horizons of human medicine. The award will be presented as part of the opening ceremony of the 81st Annual Meeting of the DGK on April 9, 2015 in Mannheim, Germany.



Essen, 19.12.2014

Invitation Inaugural Lecture PD Dr. med. Niels Voigt

On January 16, 2015 at 15:00h, PD Dr. med. Niels Voigt will give his inaugural lecture: 'Mord aus zarter Hand – Berühmte Giftmorde aus Sicht eines Pharmakologen' as part of the completion of his habilitation. The official invitation can be found here.



Essen, 17.12.2014

Merry Christmas from the Institute of Pharmacology

The Institute of Pharmacology wishes everyone a happy holiday season, merry Christmas, and all the best for 2015!



Essen, 07.11.2014

Institute of Pharmacology hosts the EUTRAF review meeting

On Tuesday, November 4, and Wednesday November 5, the Institute of Pharmacology hosted the 4th year review meeting of the “The European Network for Translational Research in Atrial Fibrillation” (EUTRAF), a European network funded as part of the FP7 program. Approximately 50 scientists traveled to Essen and, after a welcome by Prof. Dr. Forsting, vice-dean of research of the Faculty of Medicine, University Duisburg-Essen, and Prof. Dr. Heusch, director of the Institute of Pathophysiology, and chair of the West German Heart and Vascular Center, exchanged the latest results in translational atrial fibrillation research.



Essen, 31.08.2014

Ca2+/Calmodulin-dependent Protein Kinase Type-II induces maladaptive cardiac remodeling but inhibits calcineurin-induced myocardial hypertrophy

Prof. Dobrev, director of the Institute of Pharmacology contributed to a study published in Circulation by the group of Prof. Johannes Backs from the University of Heidelberg. The study by Kreusser et al. (Circulation 2014; published online on August 15) shows for the first time that both the Ca2+/calmodulin-dependent protein kinase type-II (CaMKII) δ and γ isoforms contribute to the phosphorylation of various targets, including phospholamban, the cardiac ryanodine receptor, and protein phosphatase calcineurin. Double knock-out mice lacking CaMKIIδ and CaMKIIγ were protected from cardiac dysfunction and interstitial fibrosis following pathological pressure overload. Interestingly, however, double knock-out mice did develop cardiac hypertrophy, which was found to be due to excessive calcineurin activation resulting from a lack of CaMKII-dependent phosphorylation of the auto-inhibitory site Ser411 of calcineurin. Taken together, this novel mouse model, in which CaMKII activity is specifically and completely abolished, shows that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin-dependent hypertrophy. These data suggest inhibition of CaMKII, but not calcineurin, as a promising approach to attenuate the progression of heart failure.

 Reference:

Kreusser MM, Lehmann LH, Keranov S, Hoting M-O, Kohlhaas M, Reil J-C, Neumann K, Schneider MD, Hill JA, Dobrev D, Maack C, Maier LS, Gröne H-J, Katus HA, Olson EN, Backs J (2014) The cardiac CaMKII genes δ and γ contribute redundantly to adverse remodeling but inhibit calcineurin-induced myocardial hypertrophy. Circulation, published online on Aug 15 (DOI:10.1161/CIRCULATIONAHA.114.006185).



Essen, 19.06.2014

Prof. Dobrev joins the Editorial Board of Circulation

Prof. Dobrev was asked and joined the Editorial Board of the journal Circulation. Circulation is a weekly peer-reviewed medical journal published by Lippincott Williams & Wilkins and is the official journal of the American Heart Association. The Journal ranks #1 among journals in the Cardiac & Cardiovascular Systems category and #1 among journals in the Peripheral Vascular Disease category (according to the 2012 Journal Citation Reports®, Thomson Reuters, 2013). A link to the journal can be found here: http://circ.ahajournals.org/



Essen, 06.06.2014

Dr. Niels Voigt completes habilitation

Yesterday, Dr. Niels Voigt successfully completed his habilitation with a presentation for the faculty council on generic drugs, addressing the question whether they are a true equivalent to the original preparation. In Germany, the habilitation (from Latin “habilis”, meaning "fit, proper, skillful") is the highest academic qualification a scholar can achieve by his own pursuit. It requires publication of numerous papers, as well as teaching duties. The Institute of Pharmacology congratulates Dr. Voigt with this important milestone!



Essen, 21.05.2014

Circulation Research Atrial Fibrillation Compendium

Members of the Institute of Pharmacology contributed to the most recent Compendium in Circulation Research about Atrial Fibrillation (AF). The AF compendium, which was edited by Prof. Stanley Nattel (Montreal Heart Institute, Montreal, Canada), provides a collection of review articles describing the clinical profile, genetic underpinnings, and cellular and molecular mechanisms of AF, as well as reviews of the role of the autonomic nervous system, mathematical approaches to understanding AF, and AF therapy. In particular, members of the Institute of Pharmacology wrote the article ´Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression´ and contributed to ´The Clinical Profile and Pathophysiology of Atrial Fibrillation: Relationships Among Clinical Features, Epidemiology, and Mechanisms´. According to Circulation Research, these compendia are considered “a one-stop shop for basic, translational, and clinical investigators who wish to gather a comprehensive assessment of a problem” (link)

 References:

Heijman J*, Voigt N*, Nattel S, Dobrev D (2014) Compendium: Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance and Progression. Circ Res, 114(9): 1483-1499. *equally contributed first authors

Andrade J, Khairy P, Dobrev D, Nattel S (2014) The Clinical Profile and Pathophysiology of Atrial Fibrillation: Relationships among Clinical Features, Epidemiology, and Mechanisms. Circ Res, 114(9): 1453-1468.

 


Essen, 27.03.2014

Visit Prof. Stanley Nattel

News Item Visit Nattel 2014

On Tuesday, March 25th and Wednesday March 26th, the Institute of Pharmacology was proud to have Prof. Stanley Nattel (Department of Medicine, Montreal Heart Institute and Université de Montréal and Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada) as a guest. Prof. Nattel gave a well-attended presentation as part of the Faculty of Medicine Seminar Series and was involved in numerous discussions with members of the institute about joint projects.



Essen, 18.03.2014

Visit Prof. Xander Wehrens

On Monday, March 17, long-term collaborator Prof. Xander Wehrens (Cardiovascular Research Institute, Departments of Molecular Physiology and Biophysics, and Medicine-Cardiology, Baylor College of Medicine, Houston, TX) visited the Institute of Pharmacology. Prof. Wehrens presented recent data from his lab about the role of cardiac ryanodine receptor channel regulation in atrial fibrillation and participated in discussions about ongoing collaborative projects.

 


Essen, 01.03.2014

Prof. Dr. Fritz Sörgel interviewed about athletes and doping


Essen, 14.01.2014

Cellular and Molecular Mechanisms of Atrial Arrhythmogenesis in Patients With Paroxysmal Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia with increasing incidence in aging population. Although the cellular electrophysiological abnormalities in patients with long-standing persistent AF had been studied in some detail before, the atrial-cellular pathophysiology in patients with paroxysmal AF (pAF) was largely unknown until now.

Members of the Institute of Pharmacology published a study in the most recent edition of Circulation (Voigt et al. Circulation 2014; 129(2): 145-156), showing for the first time the cellular and molecular mechanisms contributing to atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation (AF). This paper was selected for presentation in the “Best of Basic Science” Session at the Annual Meeting of the American Heart Association (Dallas, USA) and following expedited editorial consideration appeared simultaneously online on November 18, 2013, in Circulation.

In this study, simultaneous measurements of intracellular [Ca2+] and membrane current/potential in atrial cardiomyocytes from sinus rhythm and pAF patients showed that L-type Ca2+ currents and action potential durations were unaltered in pAF, pointing to the absence of typical AF-promoting atrial remodeling. However, cardiomyocytes from pAF patients showed Ca2+-handling abnormalities including enhanced diastolic sarcoplasmic reticulum (SR) Ca2+ leak and increased susceptibility to spontaneous diastolic SR Ca2+-release events, causing proarrhythmic delayed afterdepolarizations and ectopic (triggered) activities. Pharmacological and biochemical studies indicated that the susceptibility to spontaneous cellular activity in pAF was attributable to enhanced SR Ca2+ uptake, resulting from phospholamban hyperphosphorylation, and ryanodine receptor (SR Ca2+-release) channel dysregulation. Simulation studies indicated that both these factors likely contribute synergistically to aberrant diastolic SR Ca2+-release events.

Our findings constitute the first direct evidence for an important role of Ca2+-dependent ectopic activity in atrial arrhythmogenesis of pAF patients and provide insights into underlying mechanisms. The cellular and molecular mechanisms underlying abnormal Ca2+ handling in pAF are distinct from those of long-standing persistent AF patients, suggesting possible opportunities to develop tailored therapeutic approaches for pAF.

 

Reference:

Voigt N*, Heijman J*, Wang Q, Chiang DY, Li N, Karck M, Wehrens XHT, Nattel S, Dobrev D (2014) Cellular and Molecular Mechanisms of Atrial Arrhythmogenesis in Patients with Paroxysmal Atrial Fibrillation. Circulation, 129: 145-156. *equally contributed first authors



Essen, 17.12.2013

Manuscript highlighted in the Journal of the American College of Cardiology’s “The Year in Review of Clinical Cardiac Electrophysiology”

A paper written by members from the Institute of Pharmacology was highlighted in the most recent edition of the Journal of the American College of Cardiology as part of “The Year in Review of Clinical Cardiac Electrophysiology” (J. Am. Coll. Cardiol. 2013; 65:2433-2447).

In this publication (Voigt et al. Circulation. 2012;125:2059-2070), we showed that atrial myocytes isolated from right atrial appendages from patients with chronic atrial fibrillation (cAF) exhibit potentially proarrhythmic Ca2+-handling abnormalities. We assessed the underlying molecular mechanisms, and identified a causal role for Ca2+/calmodulin-dependent protein kinase-II (CaMKII)-dependent dysfunction of ryanodine receptor type-2 channels, contributing to abnormal (increased) diastolic Ca2+ leak from the sarcoplasmic reticulum and a greater incidence of spontaneous sarcoplasmic reticulum Ca2+-release events. In addition, an increased Na+/Ca2+exchanger expression in cAF resulted in an enhanced depolarizing transient-inward current for any given diastolic Ca2+-release. Together, these factors contributed to AF-promoting atrial delayed afterdepolarizations in AF patients. Our results show for the first time that delayed afterdepolarizations and related ectopic (triggered) activity may contribute to induction and maintenance of AF in patients constituting a potential target for future anti-AF therapy.

 

Reference:

Voigt N, Li N, Wang Q, Wang W, Trafford AW, Abu-Taha ISun Q, Wieland T, Ravens U, Nattel S, Wehrens XHT, Dobrev D (2012) Enhanced Sarcoplasmic Reticulum Ca2+-Leak and Increased Na+-Ca2+-Exchanger Function Underlie Delayed Afterdepolarizations in Patients with Chronic Atrial Fibrillation. Circulation, 125: 2059-2070.

 


Essen, 30.10.2013

Dr. Jordi Heijman receives CARIM Dissertation Award 2011/2012


Essen, 17.10.2013

Oxidized Ca2+/Calmodulin-dependent Protein Kinase Type-II Triggers Atrial Fibrillation in Mice

Reference:

Purohit A, Rokita AG, Guan X, Chen B, Koval O, Voigt N, Neef S, Sowa T, Gao Z, Luczak ED, Stefansdottir H, Behunin AC, Li N, El Accaoui R, Yang B, Swaminathan PD, Weiss R, Wehrens XHT, Song LS, Dobrev D, Maier L, Anderson M (2013) Oxidized CaMKII Triggers Atrial Fibrillation. Circulation, 128(16): 1748-1757.



Essen, 25.09.2013

Visit Prof Stanley Nattel and 2013 ENAFRA Leducq Meeting

On Tuesday, August 27, Prof. Stanley Nattel (Department of Medicine, Montreal Heart Institute and Université de Montréal and Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada) visited the Institute of Pharmacology. That evening, all scientific members of the institute travelled together with Prof. Nattel to Maastricht, The Netherlands, for the final meeting of the European/North-American Atrial Fibrillation Research Alliance (ENAFRA), an international network funded by Fondation Leducq.



Essen, 30.05.2013

Dr. Niels Voigt obtaines medical specialization in pharmacology and toxicology

Dr. Niels Voigt has obtained his medical specialization in pharmacology and toxicology ("Facharzt für Pharmakologie und Toxikologie").




Essen, 18.04.2013

Dr. Niels Voigt receives travel grant EWGCCE

Dr. Niels Voigt has received a travel award to attend the 37th Annual Meeting of the European Working Group on Cardiac Cellular Electrophysiology (EWGCCE) in Athens, Greece in June 2013.




Essen, 10.04.2013

MicroRNA29: A Mechanistic Contributor and Potential Biomarker in Atrial Fibrillation

Dawson et al. Circulation 2013In the most recent edition of Circulation, members of the Institute of Pharmacology contributed to a study by the group of Prof. Nattel of the Montreal Heart Institute identifying a critical role for microRNA (miR) 29b in atrial fibrotic remodeling. In the study by Dawson et al. (Circulation 2013;127:1466-1475), it was shown that miR29b is rapidly decreased in a dog model of ventricular pacing and that plasma levels of miR29b are decreased in patients with atrial fibrillation, heart failure, or both. Of note, the latter group showed significantly lower levels than those with atrial fibrillation or heart failure alone. MiR29b inhibits expression of several profibrotic genes including collagen 1A1, collagen 3A1 and fibrillin and the reduction in miR29b in fibroblasts was associated with elevated levels of these profibrotic targets. Importantly, an in vivo reduction of miR29b using adenovirus-mediated overexpression of a mir29B ‘sponge’ in mice was associated with increased fibrosis. Taken together, our work suggests for the first time that miR29b is a strong candidate to modulate atrial structural remodeling and has potential as a candidate biomarker for atrial fibrillation.

 

Reference:

Dawson K, Wakili R, Ördög B, Clauss S, Chen Y, Iwasaki Y, Voigt N, Qi XY, Sinner MF, Dobrev D, Kääb S, Nattel S (2013) MicroRNA29: A Mechanistic Contributor and Potential Biomarker in Atrial Fibrillation. Circulation, 127(14):1466-1475.




Essen, 26.03.2013

Two papers highlighted in Circulation’s ‘Most Read Articles in Arrhythmia and Electrophysiology’

Two papers co-authored by members of the Institute of Pharmacology where highlighted in the most recent edition of Circulation Editors’ Picks: Most Read Articles in Arrhythmia and Electrophysiology (Circulation. 2013; 127:e509-519).

In the first paper that was highlighted (Voigt et al. Circulation. 2012;125:2059-2070), we showed that atrial myocytes isolated from right atrial appendages from patients with chronic atrial fibrillation (AF) showed pronounced Ca2+-handling abnormalities compared to myocytes from patients in sinus rhythm. Ryanodine receptor channels showed a Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent increase in open probability in AF, contributing to increased Ca2+ leak from the sarcoplasmic reticulum and an increased incidence of spontaneous sarcoplasmic reticulum Ca2+ release events. In addition, there was an increased Na+/Ca2+ exchanger expression in cAF, contributing to an increased Ca2+/membrane potential coupling gain. Together, these factors contributed to AF-promoting atrial delayed afterdepolarizations in AF patients. These findings add to our appreciation of the phenomenon of AF begets AF, indicating that, in addition to the well-established tendency of AF to promote its own persistence by remodeling the reentrant substrate, it can enhance spontaneous ectopic (triggered) activity, which induces reentry.

 

In the second paper (Harada et al. Circulation. 2012:126;2051-2064), it was shown that transient receptor potential canonical-3 (TRPC3) channels regulate cardiac fibroblast proliferation and differentiation by controlling Ca2+ influx and activating extracellular signal-regulated kinase signaling. TRPC3 expression was increased in patients with chronic AF and various experimental AF models via an NFAT-mediated downregulation of microRNA-26, desuppressing TRPC3 expression. TRPC3 blockade inhibited the development of a vulnerable substrate for AF in a dog model of rapid atrial pacing. Together, these data suggest that TRPC3 plays an important role in structural remodeling in atrial fibrillation and is a novel potential therapeutic target.

 

References:

Voigt N, Li N, Wang Q, Wang W, Trafford AW, Abu-Taha I, Sun Q, Wieland T, Ravens U, Nattel S, Wehrens XHT, Dobrev D (2012) Enhanced Sarcoplasmic Reticulum Ca2+-Leak and Increased Na+-Ca2+-Exchanger Function Underlie Delayed Afterdepolarizations in Patients with Chronic Atrial Fibrillation. Circulation, 125: 2059-2070.

Harada M, Luo X, Qi XY, Tadevosyan A, Maguy A, Ordog B, Ledoux J, Kato T, Naud P, Voigt N, Shi Y, Kamiya K, Murohara T, Kodama I, Tardif JC, Schotten U, Van Wagoner DR, Dobrev D, Nattel S (2012) Transient Receptor Potential Canonical-3 Channel-Dependent Fibroblast Regulation in Atrial Fibrillation. Circulation, 126: 2051-2064.