Post-myocardial infarction heart failure dysregulates the bone vascular niche
Jedrzej Hoffmann1,2,3, Guillermo Luxán2,3,4, Wesley Tyler Abplanalp2,3,4
1Department of Cardiology, Center of Internal Medicine, Goethe University Frankfurt, Frankfurt, Germany.
Insights
Heart failure after myocardial infarction causes bone vascular loss in mice and humans. Anti-inflammatory therapies may prevent or reverse this bone vascular deterioration in ischemic heart disease.
Area of Science:
- Cardiovascular Biology
- Bone Biology
- Vascular Biology
Background:
- The impact of chronic diseases like heart failure on bone vasculature remains unclear.
- Myocardial infarction and subsequent heart failure significantly alter systemic physiology, potentially affecting bone health.
Purpose of the Study:
- To investigate the effects of myocardial infarction and post-infarction heart failure on bone vascular cell composition.
- To identify molecular mechanisms underlying changes in bone vasculature during ischemic heart disease.
Main Methods:
- Analysis of bone vascular cell composition in mice and humans following myocardial infarction.
- Single-cell RNA sequencing of human bone marrow endothelium.
- Genetic manipulation (overexpression and inhibition) in mouse models to study gene function.
Main Results:
- An age-independent loss of type H endothelium was observed in heart failure post-myocardial infarction in both species.
- Single-cell RNA sequencing revealed increased expression of inflammatory genes (IL1B, MYC) in human bone marrow endothelium in ischemic heart failure.
- Endothelial MYC overexpression induced type H bone endothelial cells, while NLRP3 inhibition partially rescued type H vasculature loss in mice.
Conclusions:
- Myocardial infarction and heart failure lead to detrimental changes in bone vasculature, specifically a loss of type H endothelium.
- Inflammatory pathways, particularly IL-1β and MYC, play a critical role in regulating bone vascular changes during ischemic heart disease.
- Targeting anti-inflammatory therapies presents a potential strategy to preserve or restore bone vascular function in patients with ischemic heart disease.
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.
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