Inflammatory Mutations Drive Aortic Macrophage Expansion and Proliferation
A new study in Ldlr−/− mice reveals how specific bone marrow mutations influence aortic macrophage dynamics under different lifestyle conditions.
Key finding: Mutations in Jak2V617F, Tet2, p53, and Dnmt3aR878H each uniquely alter aortic macrophage counts, proliferation, and uptake, with lifestyle factors like exercise showing variable effects.
Study Design & Methods
Researchers transplanted bone marrow carrying Jak2V617F, Tet2−/−, p53−/−, or Dnmt3aR878H mutations into Ldlr−/− mice. Aortic macrophage counts, proliferation, and bead uptake were measured across four lifestyle groups: wild-type, sedentary, SF (standard facility), and exercise. Sample sizes ranged from 4 to 11 per group.
Macrophage Counts in the Aorta
For each mutation group, macrophage counts and CD45.1 WT macrophage counts were quantified across lifestyle conditions (n=5–11 per group). Significant differences were observed between mutation and control groups, with some lifestyle conditions altering the effect.
Proliferation and Uptake
- CD45.2+ aortic macrophage proliferation was measured by flow cytometry (n=5–7 per group). Results showed mutation-specific increases in proliferation compared to wild-type controls.
- Bead uptake into aortic macrophages was quantified (n=4–7 per group), with several mutations enhancing phagocytic activity.
Blood-Aorta Correlations
A key analysis examined correlations between CD45.2 monocyte fraction in blood and CD45.2 macrophage fraction in the aorta (n=26–41 per correlation). Significant positive correlations were found, suggesting blood monocyte levels predict aortic macrophage accumulation.
Lesion Analysis in Dnmt3aR878H Mice
In mice with the Dnmt3aR878H mutation, detailed lesion assessment included:
- Lesion size, volume, and necrotic core area
- Total and CD45.2 macrophage number
- CD45.2 macrophage proliferation
Measurements (n=4–7 per group) revealed increased lesion size and macrophage proliferation compared to wild-type.
Statistical Summary
All tests were two-sided. Data are presented as mean ± s.e.m. Significance is indicated by *p<0.05, **p<0.01.
Schematics created in BioRender; McAlpine, C. https://biorender.com/1rt7rau (2026).