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. 2023 Jul 25;14:4101. doi: 10.1038/s41467-023-39586-z

Fig. 6. Cyp27a1 inhibition is atheroprotective.

Fig. 6

a–d ApoE-/- mice were placed on an atherogenic diet for 8 weeks, receiving vehicle or the cyp27a1 inhibitor GW273297X (GW) during the last 4 weeks, and atherosclerotic lesions were evaluated. Representative lipid-stained en face images of aortas (a) and lesion areas (b; percent of total surface area, n = 14). Representative lipid and haematoxylin-stained aortic root sections (c), and lesion areas (d, n = 10). e–h In parallel experiments, apoE-/- mice received vehicle, cyp27a1 inhibitor GW, or GW plus exogenous 27HC during the last 4 weeks of an 8 week period on an atherogenic diet. Representative lipid-stained en face images of aortas (e) and lesion areas (f, n = 9-13). Representative lipid and haematoxylin-stained aortic root sections (g), and lesion areas (h, n = 8-9). i–l The effect of vehicle versus GW was determined in apoE-/- background cyp27a1fl/fl and cyp27a1ΔMAC mice. Representative lipid-stained en face images of aortas (i) and lesion areas (j, n = 9-12). Representative lipid and haematoxylin-stained aortic root sections (k), and lesion areas (l, n = 9-12). Effect of cyp27a1 inhibitor on abundance of endothelial ICAM-1 (m, n) and VCAM-1 abundance (o, p) with representative images (m, o) and quantification (n, p, n = 8-9). q Effect of cyp27a1 inhibitor on monocyte recruitment, evaluated by YG bead incorporation into circulating monocytes and quantification of beads per aortic root section 24 h later. The quantitation was corrected for monocyte labeling efficiency. N = 7-8. r, s Effect of cyp27a1 inhibitor on lesion macrophage accumulation. Representative immunohistochemistry images of Mac2 staining in aortic root (r; nuclei DAPI stained) and quantification of Mac2 positive staining (s; expressed per unit lesion area, n = 8-9). Scale bar equals 100 um (c, g, k) or 50 um (m, o, r). Data are mean ± SEM, P values by two-sided Student’s t test (b, d, n, p, q and s), by Krusakal-Wallis with Dunn’s post hoc testing (f), or by ANOVA with Tukey post-hoc testing (h, j and l) are shown. Source data are provided as a Source Data file.