Post-myocardial infarction heart failure dysregulates the bone vascular niche

  • 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.
Author:Jedrzej HoffmannORCiDGND, Guillermo LuxánORCiD, Wesley Tyler AbplanalpORCiD, Simone F. GlaserORCiDGND, Tina Rasper, Ariane Fischer, Marion Muhly-Reinholz, Michael PotenteORCiDGND, Birgit AßmusORCiDGND, David JohnORCiDGND, Andreas M. ZeiherORCiDGND, Stefanie DimmelerORCiDGND
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Date of Publication (online):2021/06/25
Date of first Publication:2021/06/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/06/08
Tag:Cardiovascular biology; Molecular biology
Issue:art. 3964
Page Number:11
First Page:1
Last Page:11
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.
The single-cell RNA-seq data sets generated in this study are available at Array Express ( 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.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0