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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Animals
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Bone and Bones / blood supply*
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Bone and Bones / physiopathology
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Case-Control Studies
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Endothelial Cells / metabolism
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Endothelial Cells / pathology*
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Female
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Furans / pharmacology
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Genes, myc
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Heart Failure / etiology
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Heart Failure / physiopathology*
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Hematopoietic Stem Cells / pathology
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Humans
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Indenes / pharmacology
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Inflammation / drug therapy
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Inflammation / metabolism
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Inflammation / pathology
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Middle Aged
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Myocardial Infarction / complications
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Myocardial Infarction / genetics
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Myocardial Infarction / physiopathology*
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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Sulfonamides / pharmacology
Substances
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Furans
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IL1B protein, human
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Indenes
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Interleukin-1beta
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PECAM1 protein, human
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Platelet Endothelial Cell Adhesion Molecule-1
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Sulfonamides
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N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide