Figure 3: TILRR KO Significantly Reduces Progression of Atherosclerosis in LDLR

(A) TILRR expression levels in blood samples from patients with myocardial infarction (ST-segment elevation myocardial infarction [STEMI], light gray bar; non–ST-segment elevation myocardial infarction [NSTEMI], dark gray bar) at diagnosis, day 1, and at days 7 and 90. Values are mean ± SEM. n = 6 to 11 triplicate samples per group and time point. TILRR expression levels in each group of patient samples are compared with levels in healthy control samples (black bar). STEMI day 7, *p = 0.0442; day 90, *p = 0.0329. NSTEMI day 7, *p = 0.0445; day 90, *p = 0.0405. (B) Immunohistochemistry of an atherosclerotic plaque in the brachiocephalic artery, using a nonblocking anti-TILRR antibody, followed by a DyLight Fluor-conjugated secondary antibody, shows increased levels of TILRR expression within the lesion (top image, blue arrow), with low levels in the surrounding area (top image, white arrow) and in a healthy vessel (bottom image, white arrow). TILRR (red), nuclear stain (4'6,-diamidino-2-phenylindole, blue). Scale bar =150 μm. (C) Cross-sections of the aortic root (top) and brachiocephalic arteries (bottom) of LDLR–/– mice (control, left) and LDLR–/–/TILRR–/– mice (double knockout [DK], right), stained with Alcian blue & van Gieson. Scale bar = 500 μm (aortic root), 200 μm (brachiocephalic artery). Arrowheads point at plaques in arteries from control mice. (D, E) Quantitation, using images such as in C, shows levels of atherosclerotic plaques in (D) the brachiocephalic artery and (E) the descending aorta in DK mice and control mice. Data are expressed as percent of total area and show mean ± SEM. (D) n = 12 control mice, 15 DK mice. (E) n = 6 control mice, 9 DK mice. Levels in DK mice versus levels in control mice, (D) *p = 0.0396; (E) **p = 0.004. (F) Quantitation of collagen content following staining of sections using Martius scarlet blue. Data are expressed as percent area stained for collagen in control and DK mice and show mean ± SEM. n = 6 control mice, 6 DK mice. Levels in DK mice versus levels in control mice, ***p = 0.0004. (G) Quantitation of macrophage levels in plaques from control and DK mice following staining of sections using anti-Mac-3. Data are expressed as percent stained area and show mean ± SEM. n = 5 control, 5 DK mice. Levels in DK mice versus levels in control mice, **p = 0.003. Abbreviations as in Figure 1.