Apolipoprotein (apo) J, clusterin, is ubiquitously expressed in many tissues, and is a component of high-density lipoproteins (HDLs).There is experimental evidence that it may be anti-atherogenic through its effects on cholesterol transport, smooth muscle cell proliferation and lipid peroxidation. HDLs containing apo J and apo A-carry paraoxonase (PON1), which protects low-density lipoproteins from oxidative modification; however, the extent to which apo J affects coronary heart disease (CHD) is not known. We have developed a sandwich ELISA that enables apo J to be assayed in the range of 13-200 g/mL. Serum apo J was 52.8 0.8 g/mL (mean SEM; range, 36.0-84.3 g/mL; n 92) in healthy Japanese men, and 49.3 0.5 g/mL (34.5-72.8; n 241) in healthy Japanese women. Multiple regression of these data and results from 67 men with CHD showed that apo J concentration was unrelated to age, sex or body mass index, but was positively related to serum PON1 (p 0.001) and apo B (p 0.02) concentrations. In women, it was also positively related to blood glucose (p 0.02). After adjusting for its associations with covariates, serum apo J averaged 5.4 g/mL, lower in CHD men than in controls (p 0.003). Type 2 diabetics had higher apo J concentrations (men, 83.1 3.4 g/mL, n 64; women, 64.0 2.3 g/mL, n 46) than healthy men and women (p 0.001). In these Type 2 diabetics, apo J concentration was unrelated to PON1 concentration, but was positively related to blood glucose (p 0.01). After adjustment for its relation to blood glucose, the mean apo J concentration was similar in diabetics and healthy subjects. These findings suggest that apo J may be anti-atherogenic in humans, and that its concentration is raised by Type 2 diabetes. J Atheroscler Thromb, 2006; 13:314-322.
Acylation stimulating protein (ASP) is a fragment of the third component of complement (C3) that is generated in the presence of chylomicron, and plays a role in the synthesis of triacylglycerol by transporting free fatty acids into adipocytes. However, the precise mechanism of ASP generation, especially the role of chylomicron in ASP generation, is unknown. We examined the mechanism through which chylomicron induces ASP generation. Ultracentrifugationally separated chylomicron was incubated with normal human serum (NHS) under various conditions, and the amounts of complement activation products and ASP in the incubation mixture were determined by enzyme-linked immunosorbent assay (ELISA). Upon incubation of NHS with various amounts of chylomicron for 120 min, ASP was generated in a dose-dependent manner. The time course of the production of ASP was similar to the time course of the C3 tick-over phenomenon that occurred by depletion of factor H from the serum. The complement activation induced by chylomicron was different from the usual complement activation that occurs under the regulation of factor H and factor I with respect to the time course and the amount of ASP produced. Our results indicate that chylomicron accelerates C3 tick-over by regulating the role of factor H, leading to the overproduction of ASP.
Lentinus edodes mycelia lowers cholesterol levels and acts as an immunomodulator and tumor-inhibitor in animal models. Lentinus edodes mycelia contains eritadenine (C(9)H(11)O(4)N(5)) and glucans among other biological compounds. However, whether or not Lentinus edodes mycelia is anti-atherogenic remains unknown. We examined the effect of Lentinus edodes mycelia (L.E.M) on atherosclerosis in a rabbit model. Thirty-two Japanese white male rabbits were fed with 1.0% cholesterol for 8 weeks, then divided into groups and given 1) 1.0% cholesterol for over 8 weeks (control), 2) 1.0% cholesterol and 1.0% L.E.M for over 8 weeks, 3) 1.0% cholesterol and 2.0% L.E.M for over 8 weeks, and 4) 1.0% cholesterol and 4.0% L.E.M for over 8 weeks (n=8 each group). Total cholesterol (TC) was measured periodically throughout the experiment. After the experimental periods, the aortas were removed and atherosclerotic lesions were examined histologically, immunohistochemically and morphometrically to determine surface involvement (SI) and an atherosclerotic index (AI). Body weight and TC did not significantly differ among the four groups. Decreases in SI were significant in the 1% L.E.M (26.2+/-10.8%) and 2% L.E.M (29.3+/-15.7%) groups compared with the control (48.7+/-15.3%; p < 0.05). The AI was significantly decreased in the 1% L.E.M (6.62+/-4.31) and 2% L.E.M (7.49+/-3.49) groups compared with the control (16.96+/-9.21; p < 0.05). Foam cells aggregated in thickened intima of dietary-induced atherosclerotic lesions in the rabbit aorta. In contrast, the numbers of foam cells in the intima decreased in the experimental group. No-cholesterol-lowering action or dose-dependant effects of L.E.M were determined in this study, but atherosclerotic development was significantly inhibited, indicating that L.E.M had anti-atherogenic properties. L.E.M may inhibit atherosclerotic development in rabbit aorta and be beneficial as a nutritional supplement.
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