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PROVASC SIGNED

Cell-specific vascular protection by CXCL12/CXCR4

Total Cost €

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EC-Contrib. €

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Partnership

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 PROVASC project word cloud

Explore the words cloud of the PROVASC project. It provides you a very rough idea of what is the project "PROVASC" about.

underlying    cxcr4    expansion    receptor    types    cxcl12    rupture    endothelial    lipid    micrornas    pathology    cardiovascular    prone    inhibition    heart    regulation    neutrophil    found    humanized    chimeras    disturbed    counterbalance    giving    genome    deletion    validate    worldwide    near    lesions    promotes    protection    strategies    coding    diseases    causal    mice    conditional    variants    compartments    mechanisms    protects    marrow    recruitment    unclear    dissect    mouse    flow    ongoing    association    extend    elucidate    provasc    death    repair    sites    unravel    risk    arteries    largely    lines    lipoproteins    inflammatory    leukocyte    vulnerable    genetic    counteracting    protective    damage    poietic    models    hemato    resident    array    bone    chemokine    discover    boosting    ubiquitous    tissue    occlusion    retention    atherosclerosis    intimal    disease    atherogenic    compare    coronary    chronic    predilection    homeostasis    regeneration    axis    relevance    thrombotic    cell    versus    balance   

Project "PROVASC" data sheet

The following table provides information about the project.

Coordinator
LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN 

Organization address
address: GESCHWISTER SCHOLL PLATZ 1
city: MUENCHEN
postcode: 80539
website: www.uni-muenchen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website http://ipek.klinikum.uni-muenchen.de
 Total cost 2˙498˙250 €
 EC max contribution 2˙498˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN DE (MUENCHEN) coordinator 2˙498˙250.00

Map

 Project objective

Cardiovascular disease including coronary heart disease remains the leading cause of death worldwide. Atherosclerosis as the underlying pathology is a lipid-driven inflammatory disease of arteries giving rise to vulnerable lesions prone to rupture and thrombotic occlusion. Lesions develop at predilection sites with disturbed flow, where endothelial damage promotes intimal retention of lipoproteins and inflammatory leukocyte recruitment. Past research has largely focused on atherogenic factors and their inhibition but not on boosting a counterbalance by protective mechanisms. We have recently found that the CXCL12/CXCR4 chemokine-receptor axis protects against atherosclerosis by controlling neutrophil homeostasis and facilitating endothelial regeneration in mice. This is supported by genome-wide association studies, identifying genetic variants near CXCL12 associated with the risk of coronary heart disease. The protective regulation of endothelial repair by microRNAs also involves CXCL12/CXCR4. However, the causal and cell-specific impact of this axis remains unclear. To balance the ongoing expansion of genetic risk variants, PROVASC aims to discover/elucidate novel mechanisms for protective cell homeostasis and regeneration counteracting atherosclerosis in depth. To this end, we will dissect cell-specific effects of the CXCR4-CXCL12 axis using an array of mouse lines for conditional deletion and bone marrow chimeras to compare resident versus hemato-poietic cell compartments. We will validate a role of coding and non-coding genetic risk variants affecting CXCL12/CXCR4 in different cell types and humanized mouse models. By identifying relevant microRNAs targeting CXCL12/CXCR4, we will unravel a regulation of this axis by cell type-specific microRNAs. Given the ubiquitous relevance of CXCL12/CXCR4, we expect that the impact of such new mechanisms will extend to other chronic inflammatory diseases, allowing for tailored strategies of tissue protection and regeneration.

 Publications

year authors and title journal last update
List of publications.
2019 Esther Lutgens, Dorothee Atzler, Yvonne Döring, Johan Duchene, Sabine Steffens, Christian Weber
Immunotherapy for cardiovascular disease
published pages: , ISSN: 0195-668X, DOI: 10.1093/eurheartj/ehz283
European Heart Journal 2020-01-28
2019 Carlos Silvestre-Roig, Quinte Braster, Kanin Wichapong, Ernest Y. Lee, Jean Marie Teulon, Nihel Berrebeh, Janine Winter, José M. Adrover, Giancarlo Santiago Santos, Alexander Froese, Patricia Lemnitzer, Almudena Ortega-Gómez, Raphael Chevre, Julian Marschner, Ariane Schumski, Carla Winter, Laura Perez-Olivares, Chang Pan, Nicole Paulin, Tom Schoufour, Helene Hartwig, Silvia González-Ramos, Frit
Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
published pages: 236-240, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1167-6
Nature 569/7755 2020-01-28
2019 Esther Lutgens, Dorothee Atzler, Yvonne Döring, Johan Duchene, Sabine Steffens, Christian Weber
Immunotherapy for cardiovascular disease
published pages: , ISSN: 0195-668X, DOI: 10.1093/eurheartj/ehz283
European Heart Journal 2020-01-28
2017 Yvonne Döring, Heidi Noels, Emiel P.C. van der Vorst, Carlos Neideck, Virginia Egea, Maik Drechsler, Manuela Mandl, Lukas Pawig, Yvonne Jansen, Katrin Schröder, Kiril Bidzhekov, Remco T.A. Megens, Wendy Theelen, Barbara M. Klinkhammer, Peter Boor, Leon Schurgers, Rick van Gorp, Christian Ries, Pascal J.H. Kusters, Allard van der Wal, Tilman M. Hackeng, Gabor Gäbel, Ralf P. Brandes, Oliver Soehnlein, Esther Lutgens, Dietmar Vestweber, Daniel Teupser, Lesca M. Holdt, Daniel J. Rader, Danish Saleheen, Christian Weber
Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial IntegrityClinical Perspective
published pages: 388-403, ISSN: 0009-7322, DOI: 10.1161/CIRCULATIONAHA.117.027646
Circulation 136/4 2020-01-28
2018 Michael Lacy, Christos Kontos, Markus Brandhofer, Kathleen Hille, Sabine Gröning, Dzmitry Sinitski, Priscila Bourilhon, Eric Rosenberg, Christine Krammer, Tharshika Thavayogarajah, Georgios Pantouris, Maria Bakou, Christian Weber, Elias Lolis, Jürgen Bernhagen, Aphrodite Kapurniotu
Identification of an Arg-Leu-Arg tripeptide that contributes to the binding interface between the cytokine MIF and the chemokine receptor CXCR4
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-23554-5
Scientific Reports 8/1 2020-01-28
2018 Sophie Merckelbach, Emiel van der Vorst, Michael Kallmayer, Christoph Rischpler, Rainer Burgkart, Yvonne Döring, Gert-Jan de Borst, Markus Schwaiger, Hans-Henning Eckstein, Christian Weber, Jaroslav Pelisek
Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques
published pages: 195-206, ISSN: 0340-6245, DOI: 10.1160/TH17-04-0271
Thrombosis and Haemostasis 118/01 2020-01-28
2017 Philipp von Hundelshausen, Stijn M. Agten, Veit Eckardt, Xavier Blanchet, Martin M. Schmitt, Hans Ippel, Carlos Neideck, Kiril Bidzhekov, Julian Leberzammer, Kanin Wichapong, Alexander Faussner, Maik Drechsler, Jochen Grommes, Johanna P. van Geffen, He Li, Almudena Ortega-Gomez, Remco T. A. Megens, Ronald Naumann, Ingrid Dijkgraaf, Gerry A. F. Nicolaes, Yvonne Döring, Oliver Soehnlein, Esther Lutgens, Johan W. M. Heemskerk, Rory R. Koenen, Kevin H. Mayo, Tilman M. Hackeng, Christian Weber
Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation
published pages: eaah6650, ISSN: 1946-6234, DOI: 10.1126/scitranslmed.aah6650
Science Translational Medicine 9/384 2020-01-28
2017 Johan Duchene, Igor Novitzky-Basso, Aude Thiriot, Maria Casanova-Acebes, Mariaelvy Bianchini, S Leah Etheridge, Elin Hub, Katrin Nitz, Katharina Artinger, Kathrin Eller, Jorge Caamaño, Thomas Rülicke, Paul Moss, Remco T A Megens, Ulrich H von Andrian, Andres Hidalgo, Christian Weber, Antal Rot
Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis
published pages: 753-761, ISSN: 1529-2908, DOI: 10.1038/ni.3763
Nature Immunology 18/7 2020-01-28
2017 Anne Angelillo-Scherrer, Lina Badimon, Olivier Blanc-Brude, Marie-Luce Bochaton-Piallat, Eric Boilard, Edit I. Buzas, Andreas Caporali, Francoise Dignat-George, Paul C. Evans, Romaric Lacroix, Esther Lutgens, Daniel F. J. Ketelhuth, Rienk Nieuwland, Florence Toti, Jose Tuñon, Christian Weber, Imo E. Hoefer, Gregory Y. H. Lip, Nikos Werner, Eduard Shantsila, Hugo ten Cate, Mark Thomas, Paul Harrison, Victoria C. Ridger, Chantal M. Boulanger
Microvesicles in vascular homeostasis and diseases
published pages: 1296-1316, ISSN: 0340-6245, DOI: 10.1160/th16-12-0943
Thrombosis and Haemostasis 117/07 2020-01-28
2017 Oliver Soehnlein, Sabine Steffens, Andrés Hidalgo, Christian Weber
Neutrophils as protagonists and targets in chronic inflammation
published pages: 248-261, ISSN: 1474-1733, DOI: 10.1038/nri.2017.10
Nature Reviews Immunology 17/4 2020-01-28
2019 Emiel P.C. van der Vorst, Christian Weber
Novel Features of Monocytes and Macrophages in Cardiovascular Biology and Disease
published pages: , ISSN: 1079-5642, DOI: 10.1161/atvbaha.118.312002
Arteriosclerosis, Thrombosis, and Vascular Biology 39/2 2020-01-28
2019 Yvonne Döring, Emiel P.C. van der Vorst, Johan Duchene, Yvonne Jansen, Selin Gencer, Kiril Bidzhekov, Dorothee Atzler, Donato Santovito, Daniel J. Rader, Danish Saleheen, Christian Weber
CXCL12 Derived From Endothelial Cells Promotes Atherosclerosis to Drive Coronary Artery Disease
published pages: 1338-1340, ISSN: 0009-7322, DOI: 10.1161/circulationaha.118.037953
Circulation 139/10 2020-01-28
2018 Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T. A. Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V. Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
Mif -deficiency favors an atheroprotective autoantibody phenotype in atherosclerosis
published pages: 4428-4443, ISSN: 0892-6638, DOI: 10.1096/fj.201800058r
The FASEB Journal 32/8 2020-01-28
2017 Wolfgang Poller, Stefanie Dimmeler, Stephane Heymans, Tanja Zeller, Jan Haas, Mahir Karakas, David-Manuel Leistner, Philipp Jakob, Shinichi Nakagawa, Stefan Blankenberg, Stefan Engelhardt, Thomas Thum, Christian Weber, Benjamin Meder, Roger Hajjar, Ulf Landmesser
Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives
published pages: 2704-2716, ISSN: 0195-668X, DOI: 10.1093/eurheartj/ehx165
European Heart Journal 39/29 2020-01-28
2019 Changjun Yin, Susanne Ackermann, Zhe Ma, Sarajo K. Mohanta, Chuankai Zhang, Yuanfang Li, Sandor Nietzsche, Martin Westermann, Li Peng, Desheng Hu, Sai Vineela Bontha, Prasad Srikakulapu, Michael Beer, Remco T. A. Megens, Sabine Steffens, Markus Hildner, Luke D. Halder, Hans-Henning Eckstein, Jaroslav Pelisek, Jochen Herms, Sigrun Roeber, Thomas Arzberger, Anna Borodovsky, Livia Habenicht, Christoph J. Binder, Christian Weber, Peter F. Zipfel, Christine Skerka, Andreas J. R. Habenicht
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
published pages: 496-506, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0336-8
Nature Medicine 25/3 2020-01-28
2018 Carla Winter, Carlos Silvestre-Roig, Almudena Ortega-Gomez, Patricia Lemnitzer, Hessel Poelman, Ariane Schumski, Janine Winter, Maik Drechsler, Renske de Jong, Roland Immler, Markus Sperandio, Michael Hristov, Tanja Zeller, Gerry A.F. Nicolaes, Christian Weber, Joana R. Viola, Andres Hidalgo, Christoph Scheiermann, Oliver Soehnlein
Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis
published pages: 175-182.e5, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2018.05.002
Cell Metabolism 28/1 2020-01-28
2018 Tom T.P. Seijkens, Claudia M. van Tiel, Pascal J.H. Kusters, Dorothee Atzler, Oliver Soehnlein, Barbara Zarzycka, Suzanne A.B.M. Aarts, Marnix Lameijer, Marion J. Gijbels, Linda Beckers, Myrthe den Toom, Bram Slütter, Johan Kuiper, Johan Duchene, Maria Aslani, Remco T.A. Megens, Cornelis van ‘t Veer, Gijs Kooij, Roy Schrijver, Marten A. Hoeksema, Louis Boon, Francois Fay, Jun Tang, Samantha Baxter, Aldo Jongejan, Perry D. Moerland, Gert Vriend, Boris Bleijlevens, Edward A. Fisher, Raphael Duivenvoorden, Norbert Gerdes, Menno P.J. de Winther, Gerry A. Nicolaes, Willem J.M. Mulder, Christian Weber, Esther Lutgens
Targeting CD40-Induced TRAF6 Signaling in Macrophages Reduces Atherosclerosis
published pages: 527-542, ISSN: 0735-1097, DOI: 10.1016/j.jacc.2017.11.055
Journal of the American College of Cardiology 71/5 2020-01-28

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