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| Item Type: | Article |
|---|---|
| Title: | Post-myocardial infarction heart failure dysregulates the bone vascular niche |
| Creators Name: | Hoffmann, J., Luxán, G., Abplanalp, W.T., Glaser, S.F., Rasper, T., Fischer, A., Muhly-Reinholz, M., Potente, M., Assmus, B., John, D., 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 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 12 |
| Number: | 1 |
| 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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