Figure 14.

TDAG51 deficiency increases Prdx‐1 expression in atherosclerotic lesions and reduces intracellular superoxide levels in TDAG51^−/− peritoneal macrophages. TDAG51^−/−/ApoE^−/− (dKO) or ApoE^−/− mice were placed on control chow diet. Atherosclerotic lesions from aortic roots of (A) 25‐week‐old mice or (B) 40‐week‐old mice were sectioned and consecutive sections immunostained for Prdx‐1 and von Willebrand factor (vWF). Arrows indicate endothelium; arrowheads indicate macrophages/foam cells. Scale bar=100 μm. Representative images are shown from 5 mice per group. C, Percentage of Prdx‐1 positivity in endothelium (measured as the length of Prdx1‐positive endothelium divided by the total length of endothelium as immunostained with vWF) of 25‐ and 40‐week‐old dKO and ApoE^−/− mice. The averages of 5 sections per mouse were assessed. *P<0.05 compared with ApoE^−/− (n=8 to 9 for each genotype). D, Peritoneal macrophages isolated from TDAG51^−/− mice exhibited elevated levels of Prdx‐1 protein, as determined by immunoblotting. Data are shown as mean±SE (n=9). *P<0.05 relative to C57BL/6 (C57) macrophages. E, TDAG51^−/− peritoneal macrophages displayed lower levels of superoxide at both baseline and when subjected to 10 μmol/L 7‐ketocholesterol (7‐KC). Mean±SE from 6 independent experiments is shown. *P<0.05 relative to C57 macrophages. F, Peritoneal macrophages from C57BL/6 or TDAG51^−/− mice were incubated in the presence or absence of 20 μmol/L rosiglitazone (Rosi) for 18 hours and then immunoblotted for Prdx‐1. Data are shown as mean±SE (n=9). *P<0.05 vs C57 controls; ^P<0.05 vs respective nontreated (NT) macrophages. TDAG51 indicates T‐cell death‐associated gene 51; Prdx‐1, peroxiredoxin‐1; ApoE, apolipoprotein E; dKO, double knockout; RFU, relative fluorescence unit.