Endothelial regulators of heart failure
Final Report Abstract
In this project we aimed to identify and characterize endothelial regulators in heart failure. First we performed a screening experiment by using the transversal aortic ligation model in mouse which results in predictable heart failure. We compared isolated endothelial cells from failing heart with those of non-failing control heart we identified regulated transcripts. Here we focussed on Semaphorin 3F which was previously not described in endothelial cells. In a variety of in vitro and in vivo experiments we characterized its role in endothelial cells on the background of heart failure. A second signalling pathway that we identified to be important in endothelial cells of failing hearts is the bone morphogenetic protein (BMP) pathway. We used our expertise on this pathway to better describe its role to regulate endothelial cell behaviour in heart failure. Moreover we collaborated to investigate miRNA100 and miRNA155 in endothelial cells. In another collaboration we were involved in the characterization of a novel DARPin specifically designed to block the integrin MAC-1 which mediates the interaction between leukocytes and endothelial cells. We believe that our results contribute to the understanding of the role of endothelial cells in heart failure and may open new therapeutic avenues in the future.
Publications
- MicroRNA- 155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects During Adaptive Neovascularization. Circulation. 2015;131:1575-89
Pankratz F, Bemtgen X, Zeiser R, Leonhardt F, Kreuzaler S, Hilgendorf I, Smolka C, Helbing T, Hoefer I, Esser JS, Kustermann M, Moser M, Bode C and Grundmann S
(See online at https://doi.org/10.1161/circulationaha.114.014579) - Endothelial BMP4 Regulates Leukocyte Diapedesis and Promotes Inflammation. Inflammation. 2017;40:1862-1874
Helbing T, Arnold L, Wiltgen G, Hirschbihl E, Gabelmann V, Hornstein A, Esser JS, Diehl P, Grundmann S, Busch HJ, Fink K, Bode C and Moser M
(See online at https://doi.org/10.1007/s10753-017-0627-0) - MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy. Circ Res. 2018;122:417-432
Pankratz F, Hohnloser C, Bemtgen X, Jaenich C, Kreuzaler S, Hoefer I, Pasterkamp G, Mastroianni J, Zeiser R, Smolka C, Schneider L, Martin J, Juschkat M, Helbing T, Moser M, Bode C and Grundmann S
(See online at https://doi.org/10.1161/circresaha.117.311428) - Semaphorin 3F Promotes Transendothelial Migration of Leukocytes in the Inflammatory Response After Survived Cardiac Arrest. Inflammation. 2019;42:1252-1264
Reichert S, Scheid S, Roth T, Herkel M, Petrova D, Linden A, Weberbauer M, Esser J, Diehl P, Grundmann S, Busch HJ, Fink K, Bode C, Moser M and Helbing T
(See online at https://doi.org/10.1007/s10753-019-00985-4) - Endothelial BMP4 Promotes Leukocyte Rolling and Adhesion and Is Elevated in Patients After Survived Out-of-Hospital Cardiac Arrest. Inflammation. 2020;43:2379-2391
Arnold L, Weberbauer M, Herkel M, Fink K, Busch HJ, Diehl P, Grundmann S, Bode C, Elsasser A, Moser M and Helbing T
(See online at https://doi.org/10.1007/s10753-020-01307-9) - A DARPin targeting activated Mac-1 is a novel diagnostic tool and potential antiinflammatory agent in myocarditis, sepsis and myocardial infarction. Basic Res Cardiol. 2021;116:17
Siegel PM, Bojti I, Bassler N, Holien J, Flierl U, Wang X, Waggershauser P, Tonnar X, Vedecnik C, Lamprecht C, Stankova I, Li T, Helbing T, Wolf D, Anto-Michel N, Mitre LS, Ehrlich J, Orlean L, Bender I, Przewosnik A, Mauler M, Hollederer L, Moser M, Bode C, Parker MW, Peter K and Diehl P
(See online at https://doi.org/10.1007/s00395-021-00849-9)
