PROVASC SIGNED
Cell-specific vascular protection by CXCL12/CXCR4
Total Cost €
0EC-Contrib. €
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Explore the words cloud of the PROVASC project. It provides you a very rough idea of what is the project "PROVASC" about.
Project "PROVASC" data sheet
The following table provides information about the project.
| Coordinator |
LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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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