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Post-myocardial infarction heart failure dysregulates the bone vascular niche

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Item Type:Article
Title:Post-myocardial infarction heart failure dysregulates the bone vascular niche
Creators Name:Hoffmann, J. and Luxán, G. and Abplanalp, W.T. and Glaser, S.F. and Rasper, T. and Fischer, A. and Muhly-Reinholz, M. and Potente, M. and Assmus, B. and John, D. and Zeiher, A.M. and Dimmeler, S.
Abstract: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.
Keywords:Bone and Bones, Case-Control Studies, Endothelial Cells, Furans, Heart Failure, Hematopoietic Stem Cells, Inbred C57BL Mice, Indenes, Inflammation, Interleukin-1beta, myc Genes, Myocardial Infarction, Platelet Endothelial Cell Adhesion Molecule-1, Sulfonamides, Transgenic Mice, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:3964
Date:25 June 2021
Official Publication:https://doi.org/10.1038/s41467-021-24045-4
PubMed:View item in PubMed

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