Figure 7.

Changes in hematopoietic lamin A/C expression modulate the leukocyte immune response and extravasation capacity in vivo. Ldlr^−/− mice were reconstituted with bone marrow (BM) of the indicated genotype and were fed the high-fat diet for 2 (A and B) or 12 weeks (C). A, Representative en face immunofluorescence staining of endothelial cells (CD31⁺; green) and leukocytes (CD45.2⁺; red) in the aortic arch and quantification of CD45⁺ leukocytes per area (wild-type [WT] and Lmna^−/− mice: n=9; Lmna^tg and Lmna-OE mice: n=10; with ≈50% males and females in all experimental conditions). The mean value for each mouse was determined by averaging the number of cells present in 3 microscopic fields. Scale bar, 100 µm. B, Absolute white blood cell (WBC) counts at the end of the 2-week fat-feeding period (WT and Lmna^−/− mice: n=9; Lmna^tg and Lmna-OE mice: n=10; with ≈50% males and females in all experimental conditions). Scale bar, 100 µm. C, Representative intravital microscopy images and quantification of leukocyte extravasation into the cremaster muscle. Each value represents a different venule analyzed from transplanted Ldlr^−/− mice (n=23 WT; n=47 Lmna^−/−; n=24 Lmna^tg; and n=20 Lmna-OE). Statistical significance in A through C was assessed by the 2-tailed unpaired t test. Scale bar, 50 µm. D, Proposed mechanism for lamin A/C–dependent regulation of atherogenesis during aging. Age-related downregulation of lamin A/C levels in circulating leukocytes facilitates their extravasation into the arterial wall, thereby contributing to increased inflammation and the progression of atherosclerosis.