TY  - JOUR
A1  - Hoffmann, Jedrzej
A1  - Luxán, Guillermo
A1  - Abplanalp, Wesley Tyler
A1  - Glaser, Simone F.
A1  - Rasper, Tina
A1  - Fischer, Ariane
A1  - Muhly-Reinholz, Marion
A1  - Potente, Michael
A1  - Aßmus, Birgit
A1  - John, David
A1  - Zeiher, Andreas M.
A1  - Dimmeler, Stefanie
T1  - Post-myocardial infarction heart failure dysregulates the bone vascular niche
T2  - Nature Communications
N2  - The regulation of bone vasculature by chronic diseases, such as heart failure is unknown. Here, we describe the effects of myocardial infarction and post-infarction heart failure on the bone vascular cell composition. We demonstrate an age-independent loss of type H endothelium in heart failure after myocardial infarction in both mice and humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium, showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Endothelial-specific overexpression of MYC was sufficient to induce type H bone endothelial cells, whereas inhibition of NLRP3-dependent IL-1β production partially prevented the post-myocardial infarction loss of type H vasculature in mice. These results provide a rationale for using anti-inflammatory therapies to prevent or reverse the deterioration of bone vascular function in ischemic heart disease.
KW  - Cardiovascular biology
KW  - Molecular biology
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63600
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-636004
SN  - 2041-1723
N1  - We thank Eva-Maria Rogg, Bianca Schuhmacher, and Marga Müller-Ardogan for excellent technical support and patient care and Halvard Bönig for support in establishing and validating human flow cytometry panels. The study was supported by the German Research Foundation (SFB 834; project B6 to B.A., J.H., and A.M.Z.; project B1 to S.D.), the German Center for Cardiovascular Research, Berlin, Germany, to S.D. and A.M.Z. and the Dr. Rolf M. Schwiete Stiftung to S.D. The work by M.P. was supported by the European Research Council Consolidator Grant EMERGE (773047). Open Access funding enabled and organized by Projekt DEAL.
N1  - The single-cell RNA-seq data sets generated in this study are available at Array Express (https://www.ebi.ac.uk/arrayexpress) with the following accession numbers: E-MTAB-10432 and E-MTAB-10448. All other data are included within the article, source data, and supplementary data can be made available upon request. Source data are provided with this paper.
VL  - 12
IS  - art. 3964
SP  - 1
EP  - 11
PB  - Nature Publishing Group UK
CY  - [London]
ER  -