Fig. 8: IL-6 and versican derived from bone marrow endothelial cells boost leukocytosis in atherosclerosis and MI.
From: Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease
a, Experimental outline. Atherosclerosis was induced in Cdh5CreERT2 and Cdh5CreERT2;Il6fl/fl mice by injecting PCSK9-AAV and administering a high-cholesterol diet (HCD) for 12 weeks. Both groups received tamoxifen injections 2 weeks before AAV injection and the start of the high-cholesterol diet. b, Flow plots, frequency and proliferation of SLAM–LSK in Cdh5CreERT2 and Cdh5CreERT2;Il6fl/fl mice with atherosclerosis (n = 10 Cdh5CreERT2 mice, n = 8 Cdh5CreERT2;Il6fl/fl mice for numbers; n = 8 mice per group for BrdU; two-tailed Welch’s t-test). c, Blood monocyte and neutrophil numbers (n = 9 Cdh5CreERT2 mice, n = 7 Cdh5CreERT2;Il6fl/fl mice; two-tailed Mann–Whitney test). d,e, Competitive bone marrow-transplantation assay. Bone marrow mononuclear cells (BMNCs) were isolated from Cdh5CreERT2 and Cdh5CreERT2;Il6fl/fl mice with atherosclerosis and mixed with BMNCs from naive CD45.1 mice in equal proportions before transplantation into lethally irradiated CD45.2 recipients. Flow plot (d) and time course (e) of blood leukocyte chimerism, showing reduced contribution from Cdh5CreERT2;Il6fl/fl donors (n = 8 recipient mice per group, two-tailed Welch’s t-test for percent CD45.2 at week 16). f, Experimental outline. Cdh5CreERT2 and Cdh5CreERT2;Vcanfl/fl mice received tamoxifen injections 2 weeks before MI. g,h, Flow plots, numbers and proliferation of bone marrow SLAM–LSK (g) and blood myeloid cells (h) in Cdh5CreERT2 controls and Cdh5CreERT2;Vcanfl/fl mice, all 3 d after MI (n = 8 mice per group, two-tailed Mann–Whitney test). i,j, Competitive bone marrow-transplantation assay. BMNCs were taken from Cdh5CreERT2 and Cdh5CreERT2;Vcanfl/fl mice, both 3 d after MI, and mixed with BMNCs from naive CD45.1 mice in equal proportions before transplantation into lethally irradiated CD45.2 recipients. Flow plot (i) and time course (j) of blood leukocyte chimerism, showing reduced contribution from Cdh5CreERT2;Vcanfl/fl donors (n = 8 recipient mice per group, two-tailed Welch’s t-test for percent CD45.2 at week 16). Data are displayed as mean ± s.e.m.
