Fig. 3: LDAH deficiency increases atherosclerosis development and decreases plaque stability.

A, B Global LDAH deficiency. At 8 weeks of age mice were switched from regular chow to WD for 12 weeks, until age 20 weeks. Images and charts show representative H&E images of aortic root sections and quantification of atherosclerotic lesion size in Ldah^+/+Apoe^−/− (WT, gray dots) vs. Ldah^−/−Apoe^−/− (KO, red dots) female (n = 12 WT and 11 K0, *P = 0.0154) (A) and male (n = 13 WT and 12 KO, **P = 0.0051) (B) littermates. C Bone-marrow specific LDAH deficiency. Eight-week-old Apoe^−/− mice were transplanted with bone-marrow cells isolated from Ldah^−/−Apoe^−/− mice (KO BMT, gray dots, n = 12) or Ldah^+/+Apoe^−/− mice (WT BMT, red dots, n = 13) *P = 0.0309. Mice were fed regular chow for an additional 4 weeks after transplant and at 12 weeks of age mice were switched to a WD for 12 additional weeks. D Representative images and quantification of TUNEL+ cells (pointed by arrows) (n = 14 WT and 16 KO females, ****P < 0.0001; 17 WT and 14 KO males, **P = 0.0018; 12 WT and 13 KO BMT recipients, ***P = 0.0004). E Representative H&E images with necrotic areas outlined by black dashed line, and quantification of necrosis (n = 13 WT and 14 KO females, **P = 0.005; 11 WT and 9 KO males, **P = 0.0087; 13 WT and 12 KO BMT recipients, **P = 0.0064). F Representative Masson’s Trichrome images with lesion areas outlined in yellow, and quantification of collagen (blue) (n = 10 WT and 12 KO females, ****P < 0.0001; 9 WT and 10 KO males, *P = 0.0346; 13 WT and 10 KO BMT recipients, *P = 0.0121). G Representative immunostaining with anti-Mac3 (brown), and quantification of Mac3-positive areas (n = 10 WT and 12 KO females, ***P = 0.0009; 11 WT and 11 KO males, **P = 0.0029; 13 WT and 10 KO BMT recipients, **P = 0.0062). All representative images in D–G correspond to lesions of WT females vs. females with LDAH deficiency. All gray bars in Figures D-F represent WT mice, and red bars represent KO mice. All scale bars: 200 μm. Data are presented as mean ± SEM of independent samples. Comparisons were performed by two-tailed Mann-Whitney U test for male lesions (panel B), apoptosis in male and female mice, and collagen in BMT mice. Two-tailed Welch’s t-test was used for apoptosis in BMT mice. All other comparisons were performed using two-tailed unpaired t-test. Source data are provided as a Source Data file.