TY  - INPR
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  - John, David
A1  - Aßmus, Birgit
A1  - Zeiher, Andreas M.
A1  - Dimmeler, Stefanie
T1  - Effects of post-myocardial infarction heart failure on the bone vascular niche
T2  - bioRxiv
N2  - Bone vasculature provides protection and signals necessary to control stem cell quiescence and renewal1. Specifically, type H capillaries, which highly express Endomucin, constitute the endothelial niche supporting a microenvironment of osteoprogenitors and long-term hematopoietic stem cells2–4. The age-dependent decline in type H endothelial cells was shown to be associated with bone dysregulation and accumulation of hematopoietic stem cells, which display cell-intrinsic alterations and reduced functionality3. 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 vascular bone cell composition. We demonstrate an age-independent loss of type H bone endothelium in heart failure after myocardial infarction in both mice and in 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. Inhibition of NLRP3-dependent IL-1β production partially prevents 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 vascular bone function in ischemic heart disease.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72762
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-727623
UR  - https://www.biorxiv.org/content/10.1101/2020.05.29.123711v1
IS  - 2020.05.29.123711 Version 1
PB  - bioRxiv
ER  -