Oxidized LDL

Background. – Recent studies showed the intervention of free radicals in the genesis of chronic complications of diabetes mellitus. It has been established that oxidized LDL are involved in the genesis of arteriosclerosis.Aim. – Based on this framework, we evaluated metabolic parameters, anti-oxidant and oxidant status in non-insulin dependent diabetes mellitus (NIDDM).Methods. – This study has been conducted on 39

Oxidation of low density lipoproteins (LDL) in- duced by incubation with Cu 2 1 ions results in the formation of a heterogeneous group of aldehydic adducts on lysyl resi- dues (Lys) of apolipoprotein B (apoB) that are thought to be responsible for the uptake of oxidized LDL (oxLDL) by macrophages. To define the structural and chemical criteria governing such cell

Theoretical probabilistic kinetic model has been applied to describe the measurements of several oxidation markers as a function of time, during slow oxidation of low-density lipoprotein (LDL). It has been demonstrated that such a process could be described as tocopherol-mediated peroxidation (TMP), initiated and sustained by the action of copper ions, present in LDL in trace amounts. In that process concentration of alpha-tocopherol remains essentially unaltered. Tocopherol and copper ions act as catalysts, oscillating between the oxidized and reduced states. The fitting of the theoretical model to the experimental data resulted in determination of the numerical values for the kinetic parameters. It has been found that the parameter values used for the fitting of the data collected for a number of samples from various donors differ rather little. The kinetic chain length of 1.3 (in presence of co-antioxidants) and 2.9 (in the absence of co-antioxidants) is shorter than found by others. The difference probably comes from the much lower concentration of copper ions in our systems (about 0.1 ion per LDL particle).

Abstract—Mice expressing human apolipoprotein A-IV (apoA-IV) mainly in the intestine were obtained in an apolipoprotein E–deficient (apoE 0 ) background (apoA-IV/E 0 mice). Quantification of aortic lesions and plasma lipid determination showed that compared with their control ...

BackgroundOxidative stress-induced endothelial dysfunction and oxidized low-density lipoprotein (LDL) might play a key role in the pathogenesis of atherosclerosis. We recently identified a vascular endothelial scavenger receptor, collectin placenta 1 (CL-P1), which acts as a receptor for oxidized LDL as well as for microbes.

Background Oxidized LDL (oxLDL) inhibits angiogenesis in part by downregulating endothelial basic fibroblast growth factor (bFGF). To determine the mechanism of the downregulation, we investigated the signal transduction pathway involving potential phospholipid mediators. Methods and Results Cultured bovine aortic endothelial cells were incubated with PBS (lipoprotein-free control), LDL, or copper oxLDL under serum-free conditions. At 24 hours, oxLDL (50 μg/mL) decreased bFGF mRNA (Northern blot), bFGF protein (Western blot and ELISA), and concomitant DNA synthesis, all by 40% to 50% compared with PBS. LDL had no effect. Pretreating the cells with 100 ng/mL pertussis toxin (PTX) for 18 hours before oxLDL exposure almost completely blocked the inhibitory effects of oxLDL. In contrast, inhibiting other major cellular signal transduction pathways with PD-98059 (mitogen-activated protein kinase kinase inhibitor), HA-1004 (inhibitor of cGMP- and cAMP-dependent protein kinase), or Ro-31-8...

An imperative event in foam cells generation in the atherosclerosis is the LDL oxidation. When this particle is oxidized they are recognized by macrophage which begins to convert on reactive cells producing growing factor and inducing replication of smooth muscle cells. The glication and oxidative processes increase the LDL electronegativity and its inflammatory effect; therefore inhibit that process as much

Background: Arctigenin, a lignan polyphenol found in burdock sprout, is a potent activator of AMP-activated protein kinase (AMPK) and has beneficial effects on metabolic disorders in mice. This highlights the potential value of arctigenin for the reduction of oxidized LDL (oxLDL) by activation of AMPK in human, but not well elucidated.

Methods: We conducted a placebo-controlled, randomized, double-blind, parallel-groups study in healthy adults to investigate the effects of 12 weeks of a continuous intake of burdock sprout extract enriched with arctigenin on lipid metabolism. The subjects were 100 Japanese individuals with low-density lipoprotein cholesterol (LDL-C) < 140 mg/dl and a body mass index (BMI) of 23–30 kg/m2 who were randomly assigned to receive either burdock sprout extract (test food) or a placebo. The test food was encapsulated burdock sprout extract containing approximately 40 mg of arctigenin equivalent per day, and the placebo capsules contained no burdock sprout extract. The subjects consumed the assigned foods daily for 12 weeks.

Results: The test food significantly suppressed oxLDL after 12 weeks in subjects with a body mass index (BMI) of 25 kg/m2 or higher. The test food inhibited an increase in the FIB-4 index (liver fibrosis index), an indicator of hepatic fibrosis. Pearson’s correlation coefficient analysis revealed a significant correlation between oxLDL and FIB-4 index changes, suggesting that the test food suppressed the rise in the FIB-4 index by controlling oxLDL while maintaining the platelet count.

Conclusions: We conclude that the consumption of a burdock sprout supplement containing arctigenin is effective in suppressing oxLDL, which may prevent liver fibrosis.

Clinical trial registration: UMIN000036664

Keywords: arctigenin, burdock sprout, oxidized LDL, FIB-4 index, randomized controlled study

The incidence of atherosclerosis can be modified by diet, and plant-derived proteins have a beneficial effect, but the underlying mechanisms remain unclear. It has been suggested that oxidized LDL (oxLDL) and autoantibodies against oxLDL are important in the development of atherosclerosis. We analyzed these factors in rabbits fed a nonpurified diet supplemented with high cholesterol (10.0 g/kg) containing either 270.0 g/kg casein (CAS, n = 10) or 270.0 g/kg soy protein isolate (SPI, n = 10) for 2 mo. Plasma and purified serum LDL from rabbits were analyzed at d 0, 15, 30, 45 and 60 of treatment, and the size of atherosclerotic lesions was evaluated at d 60 of treatment. CAS-fed rabbits had significantly higher plasma cholesterol at d 15-45 and LDL cholesterol levels at d 15 and 30. Levels of trilinolein and phosphatidylcholine hydroperoxides were higher in the LDL fraction of rabbits fed CAS than in those fed SPI. Also, CAS-fed rabbits had higher levels of highly oxidized LDL [monoc...

Lipid peroxidation and oxidative modification of low-density lipoprotein (LDL) have been implicated as causal factors in the pathogenesis of atherosclerosis, and prevention of LDL oxidation by antioxidants may be an effective strategy to inhibit the progression of the disease. We investigated the effects of the reduced form of vitamin C (L-ascorbic acid, AA) and its two-electron oxidation product (dehydro-L-ascorbic acid, DHA) upon metal ion-dependent oxidative modification of human LDL. We found that low micromolar concentrations of both AA and DHA protect LDL against oxidation induced by Cu2+ or by hemin and hydrogen peroxide. In a dose-dependent manner, AA and DHA prevented the initiation of lipid peroxidation in LDL, as determined by a sensitive and selective assay for lipid hydroperoxides utilizing HPLC with chemiluminescence detection. AA and DHA also preserved the LDL-associated antioxidants alpha-tocopherol, beta-carotene, and lycopene, but not ubiquinol-10. Furthermore, AA ...

Studies with mice have revealed that increased expression of apolipoprotein A-II (apoA-II) results in elevations in high density lipoprotein (HDL), the formation of larger HDL, and the development of early atherosclerosis. We now show that the increased size of HDL results in part from an inhibition of the ability of hepatic lipase (HL) to hydrolyze phospholipids and triglycerides in the HDL and that the ratio of apoA-I to apoA-II determines HDL functional and antiatherogenic properties. HDL from apoA-II transgenic mice was relatively resistant to the action of HL in vitro. To test whether HL and apoA-II influence HDL size independently, combined apoA-II transgenic/HL knockout (HLko) mice were examined. These mice had HDL similar in size to apoA-II transgenic mice and HLko mice, suggesting that they do not increase HDL side by independent mechanisms. Overexpression of apoA-I from a transgene reversed many of the effects of apoA-II overexpression, including the ability of HDL to serv...

Aims/hypothesis. Oxidized LDL is immunogenic and immune complexes formed by oxidized LDL and corresponding antibodies are pro-atherogenic and pro-inflammatory. Considering that macroalbuminuria is a risk factor for coronary heart disease and that ...