Effects of Post-Myocardial Infarction Heart Failure on the Bone Vascular Niche

Hoffmann, J.; Luxan, G.; Abplanalp, W. T.; Glaser, S.-F.; Rasper, T.; Fischer, A.; Muhly-Reinholz, M.; John, D.; Assmus, B.; Zeiher, A. M.; Dimmeler, S.

doi:10.1101/2020.05.29.123711

bioRxiv · 10.1101/2020.05.29.123711

Effects of Post-Myocardial Infarction Heart Failure on the Bone Vascular Niche

Hoffmann, J.·Luxan, G.·Abplanalp, W. T.·Glaser, S.-F.·Rasper, T.·Fischer, A.·Muhly-Reinholz, M.·John, D.·Assmus, B.·Zeiher, A. M.·Dimmeler, S.

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Abstract

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-1{beta} 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.

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Hoffmann, J., Luxan, G., Abplanalp, W. T., Glaser, S.-F., Rasper, T., Fischer, A., Muhly-Reinholz, M., John, D., Assmus, B., Zeiher, A. M., Dimmeler, S.. 2020-05-30. Effects of Post-Myocardial Infarction Heart Failure on the Bone Vascular Niche. https://doi.org/10.1101/2020.05.29.123711

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