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American Heart Association

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Final ID: P-128

Endothelial Nitric Oxide Determines Hematopoietic Cell Fate and Osteoclastogenesis By Modulating CSF1 During Hypertension

Abstract Body: Introduction: Loss of endothelial nitric oxide (NO) is common in hypertension (HTN). The bone marrow niche contains endothelial cells; however, how endothelial NO affects hematopoiesis and bone in HTN remains undefined.
Hypothesis: We hypothesized that NO loss in HTN drives hematopoiesis in the bone marrow, later favoring osteoclastogenesis and bone resorption.
Methods and Results: By microcomputed tomography, eNOS deficient mice (eNOS-/-) had reduced femoral cortical area (Figure 1A) and trabecular bone volume fraction (Figure 1B) compared to wildtype mice (WT). Flow cytometry showed that granulocyte-monocyte (Figure 1C) and common lymphoid progenitors (Figure 1D) were markedly higher in eNOS-/- than in WT. mRNA analysis revealed loss of endothelial NO increased expression of cathepsin K (Ctsk), colony stimulating factor-1 receptor (CSF1R), and tartrate resistant acid phosphatase (TRAP) in the bone marrow. We exposed murine bone-marrow endothelial cells (BMECs) to 5% (normotension), 5% with L-NAME, or 10% (HTN) cyclic strain. Compared to 5% strain, BMECs exposed to L-NAME or 10% strain exhibited markedly increased CSF1 production, an essential cytokine for myelopoiesis and osteoclastogenesis (Figure 1E and F). In coculture experiments, we also found that macrophages cultured with BMECs undergoing 5% strain with L-NAME or 10% strain exhibited higher expression of Ctsk, CSF1R, and TRAP, indicating osteoclast formation.
Conclusion: Endothelial NO likely inhibits osteoclastogenesis and bone resorption. The loss of NO through mechanical stretch or inhibiting eNOS increases CSF1 production and hematopoiesis. This shows a potential mechanism by which NO loss leads to pathological hematopoiesis and bone resorption during HTN.
  • Hennen, Elizabeth  ( Vanderbilt University , Nashville , Tennessee , United States )
  • Nyman, Jeffry  ( Vanderbilt University Medical Cente , Nashville , Tennessee , United States )
  • Harrison, David  ( Vanderbilt University Medical Cente , Nashville , Tennessee , United States )
  • Author Disclosures:
    Elizabeth Hennen: DO NOT have relevant financial relationships | Jeffry Nyman: DO NOT have relevant financial relationships | David Harrison: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

Poster Session 1: TAC Competition and Reception

Thursday, 09/05/2024 , 05:30PM - 07:00PM

TAC Poster Session Competition

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