High-density lipoprotein prevents SAA-induced production of TNF-α in THP-1 monocytic cells and peripheral blood mononuclear cells

In this study, we evaluated whether human serum and lipoproteins, especially high-density lipoprotein (HDL), affected serum amyloid A (SAA)-induced cytokine release. We verified the effects of SAA on THP-1 cells in serum-free medium compared to medium containing human serum or lipoprotein-deficient serum. SAA-induced tumour necrosis factor-alpha (TNF-α) production was higher in the medium containing lipoprotein-deficient serum than in the medium containing normal human serum. The addition of HDL inhibited the SAA-induced TNF-α release in a dose-dependent manner. This inhibitory effect was specific for HDL and was not affected by low-density lipoprotein or very low-density lipoprotein. In human peripheral blood mononuclear cells, the inhibitory effect of HDL on TNF-α production induced by SAA was less pronounced. However, this effect was significant when HDL was added to lipoprotein-deficient medium. In addition, a similar inhibitory effect was observed for interleukin-1 beta release. These findings confirm the important role of HDL and support our previous hypothesis that HDL inhibits the effects of SAA during SAA transport in the bloodstream. Moreover, the HDL-induced reduction in the proinflammatory activity of SAA emphasizes the involvement of SAA in diseases, such as atherosclerosis, that are characterized by low levels of HDL.

Efecto de la terapia hormonal de reemplazo que incluye un progestágeno sobre la sensibilidad a la insulina y el perfil de lípidos en la mujer en etapa de posmenopausia / Effects of hormone replacement therapy including a progestin on insulin sensitivity and lipid profile in postmenopausal women

Background: The cardiovascular protective properties of hormone replacement therapy can be hampered when a progestin is used. Aim: To assess the effects of hormone replacement therapy with progestins on insulin sensitivity and lipid profile. Patients and methods: Twelve healthy postmenopausal women aged 45 to 55 years old were studied. Blood lipids and insulin sensitivity, determined using the insulin tolerance test, were measured at baseline and after three months of hormone replacement therapy using conjugated estrogens, 0.625 mg/day and medroxyprogesterone acetate, 5 mg/day. Results: The glucose disappearance constant was higher after the treatment period than at baseline (5.3ñ0.8 and 4.7ñ0.8 percent/min respectively, p = 0.005). Serum LDL cholesterol was also lower at the end of treatment period (124.5 ñ 30.2 and 140ñ25.4 mg/dl respectively, p = 0.019). Conclusions: In this group of postmenopausal women, a period of three months of hormone replacement therapy with a progestin improved insulin sensitivity and lowered LDL cholesterol levels

Plasma clearance and biodistribution of oxidatively modified 99mTc-Beta-VLDL in rabbits

The biodistribution and removal from plasma (measured as fractional clerance rate, FCR, per hour) of native and oxidatively modified (99m)technetium-labeled Beta-very low density lipoprotein ((99m)Tc-Beta-VLDL)) were investigated in hypercholesterolemic (HC) and control (C) three-month old New Zealand rabbits. The intracellular accumulation of Beta-VLDL labeled with (99m)Tc was studied in vitro in THP-1 cells and monocyte-derived macrophages isolated from rabbits. After intravenous injection into C rabbits, copper-oxidized Beta-VLDL ((99m)Tc-ox-Beta-VLDL)) was cleared from the circulation faster (0.362 + 0.070/h) than native Beta-VLDL ((99m)Tc-nat-Beta-VLDL, 0.241 + 0.070/h)). In contrast, the FCR of (99m)Tc-ox-Beta-VLDL in HC rabbits was lower (0.100 + 0.048/h) than that of (99m)Tc-nat-Beta-VLDL (0.163 + 0.043/h). The hepatic uptake of radiolabeled lipoproteins was lower in HC rabbits (0.114 + 0.071 percent injected dose/g tissue for (99m)Tc-nat-Beta-VLDL and 0.116 + 0.057 percent injected dose/g tissue for (99m) Tc-ox-Beta-VLDL) than in C rabbits (0.301 + 0.113 percent injected dose/g tissue for (99m)Tc-nat-Beta-VLDL and 0.305 + 0.149 percent injected dose/g tissue for ((99m)Tc-ox-Beta-VLDL). The uptake of (99m)Tc-nat-Beta-VLDL and (99m)Tc-ox-Beta-VLDL by atherosclerotic aorta lesions isolated from HC rabbits ((99m)Tc-nat-Beta-VLDL:0.033 + 0.012 percent injected dose/g tissue and (99m)Tc-ox-Beta-VLDL: 0.039 + 0.017 percent injected dose/g tissue) was higher in comparison to that of non-atherosclerotic aortas from C rabbits (99m)Tc-nat-Beta-VLDL: 0.023 + 0.010 percent injected dose/g tissue and (99m)Tc-ox-Beta VLDL: 0.019 + 0.010 percent injected dose/g tissue). However, (99m) Tc-nat-Beta-VLDL and (99m)Tc-ox-Beta-VLDL were taken up by atherosclerotic lesions at similar rates. In vitro studies showed that both monocyte-derived macrophages isolated from rabbits and THP-1 macrophages significantly internalized more (99m)Tc-ox-Beta-VLDL than (99m)Tc-nat-Beta-VLDL. These results indicate that in cholesterol-fed rabbits (99m)Tc-ox-Beta-VLDL is slowly cleared from plasma and accumulates in atherosclerotic lesions. However, although the extent of in vitro uptake of (99m)Tc-ox-Beta-VLDL by macrophages was high, the in vivo accumulation of this radiolabeled lipoprotein by atherosclerotic lesions did not differ from that of (99m)Tc-nat-Beta-VLDL.

Studies on the inhibitory activities of human serum lipoproteins for Japanese encephalitis virus.

Human serum lipoproteins were purified by ultracentrifuging and their concentrations adjusted as required to be within the normal male/female serum range for all assays. The activities in inhibition of hemagglutination (HAI) for Japanese encephalitis virus were--low density lipoprotein (LDL) greater than very low density lipoprotein (VLDL) greater than high density lipoprotein (HDL). Heating (56 degrees C/30 minutes) caused the LDL titer to fall and freeze-thawing (20 degrees C/room temperature) the VLDL titer to rise slightly, possibly as a result of alteration in lipoprotein structure. The additon of lipoprotein depleted serum appeared to dampen these effects and there was no nett change in titer when it was added to a lipoprotein mixture. Similarly, unfractionated normal serum showed no significant change in titer after these treatments. The lipoproteins lacked significant virus neutralizing (VN) activity and this remained so in spite of fluctuations in HAI titer after heating and freeze-thawing.