Zuyuan Xu

Lack of evidence for antiatherogenic effects of wheat bran or corn bran in apolipoprotein E-knockout mice.

Epidemiological studies have suggested that intake of whole grains is inversely associated with coronary artery disease. The mechanisms, however, are not completely clear. We tested the hypothesis that intake of wheat bran or corn bran would (1) increase the plasma concentration of phenolic antioxidants and (2) reduce atherosclerosis in apo E-knockout mice. Apo E-knockout (E-KO) mice were fed for 18 weeks with a 0.1% cholesterol-supplemented diet in the absence of grain brans or the presence of 1.7% yellow dent corn bran or 3.3% hard red spring wheat bran. The concentration of antioxidant ferulic acid in plasma and urine was measured by HPLC to monitor the bioavailability of grain phenolics. Plasma lipoprotein profiles were determined by a combination of HPLC and online enzymatic methods. Urinary 15-isoprostane F(2t), an in vivo LDL oxidation biomarker, and atherosclerotic lesions were analyzed by ELISA and histological methods, respectively. Dietary supplementation with corn or wheat bran resulted in a 4- and 24-fold increase, respectively, in urinary excretion of ferulic acid. The urinary recovery rate of ferulic acid from the two brans in apo E-KO mice was approximately 1.9-2.9%. Dietary corn bran but not wheat bran also significantly increased the concentration of total ferulic acid in plasma. Nevertheless, the supplementation with either bran product for 18 weeks did not significantly alter the urinary excretion of 15-isoprostane F(2t), change the lipoprotein profiles, nor reduce the atherosclerotic lesion development in this animal model. The results suggest that phenolic antioxidants from the two types of bran may not be sufficient to reduce atherosclerosis in this animal model.

Pro-atherogenic effects of probucol in apo E-KO mice may be mediated through alterations in immune system: Parallel alterations in gene expression in the aorta and liver

OBJECTIVE To establish underlying molecular mechanisms of pro-atherogenic effects of probucol in apo E-KO mice. METHODS Affymetrix Gene Chip System, GenMAPP/MAPPFinder software and real-time PCR techniques were used to identify alterations in gene expression and biological pathways in the liver and aorta of both male apo E-KO and male wild-type mice treated with or without probucol (1%, w/w) for 18 weeks. Plasma levels of lipids, cytokines, liver function test, and the extent of atherosclerosis and liver histology were examined. RESULTS AND CONCLUSIONS Probucol treatment paradoxically reduced plasma cholesterol levels, increased plasma cytokine levels and atherogenesis in apo E-KO mice. Three hundred and sixty genes/transcripts and 110 biological processes were significantly differentially expressed in the liver of probucol-treated apo E-KO mice. The response to biotic stimulus, immune response and inflammatory response were the most prominent processes expressed in the liver. The expression of 60 of these genes involved in immune response including inflammatory responses, antigen presentation, humoral immune response, immune cell activation, innate immune response, and regulation of immune response was over-expressed. Many of these genes were also over-expressed in the aorta of probucol-treated apo E-KO mice. Such effects of probucol were not observed in the liver and aorta of wild-type mice. A significant interaction between apo E deficiency and probucol treatment was observed. Histological examinations showed a significant infiltration of inflammatory cells in the liver of probucol-treated apo E-KO mice, but not in C57BL/6 mice. These findings suggest that probucol-induced atherogenesis may be mediated through a pro-inflammatory state.