scholarly journals Levels of Oxidized LDL, Estrogens, and Progesterone in Placenta Tissues and Serum Paraoxonase Activity in Preeclampsia

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Şerefden Açıkgöz ◽  
Ülkü Özmen Bayar ◽  
Murat Can ◽  
Berrak Güven ◽  
Görkem Mungan ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Trophoblast Invasion ◽  
Pon1 Activity ◽  
Serum Paraoxonase ◽  
The Relationship ◽  
Serum Pon1 Activity

In vitro literature studies have suggested that atherosclerotic oxidized low density lipoprotein (OxLDL) inhibits trophoblast invasion. The objective of this study was to determine the levels of OxLDL and to examine the relationship between antioxidative estradiol, estriol, and prooxidative progestin in normal and preeclamptic placental tissues and measure the serum activity of antioxidative paraoxonase (PON1). The study included 30 preeclamptic and 32 normal pregnant women. OxLDL was determined with ELISA, estradiol, unconjugated estriol, and progesterone that were determined with chemiluminescence method in placental tissues. Serum PON1 activity was determined with spectrophotometric method. Levels of OxLDL (), estriol (), estradiol (), and progesterone () were lower in the placental tissues of preeclamptic group compared to the normal pregnant women. Serum PON1 activity was higher in preeclamptic group () and preeclamptic group without intrauterine growth restriction () compared to normal pregnant women. Tissue estriol of preeclamptic group without/with IUGR (, ) was lower than the normal group. Results of our study suggest that the events leading to fetoplacental insufficiency lead to a reduction in the levels of estriol limit deposition of OxLDL in placental tissues. The serum PON1 activity is probably important in the inhibition of OxLDL in preeclampsia.

scholarly journals Increased oxidized-LDL levels and arylesterase activity/HDL ratio in ESRD patients treated with hemodialysis

2012 ◽  
Vol 35 (3) ◽  
pp. 144 ◽  
Author(s):  
Abdolkarim Mahrooz ◽  
Mehryar Zargari ◽  
Omid Sedighi ◽  
Hamed Shaygani ◽  
Ghorban Gohari
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pon1 Activity ◽  
Control Group ◽  
Control Subjects ◽  
Increased Risk ◽  
The Status ◽  
Serum Paraoxonase ◽  
Esrd Patients

Purpose: Investigations, in which oxidized-low density lipoprotein (ox-LDL), serum paraoxonase (PON1) and homocysteine (Hcy) are considered together as important agents involved in the development of oxidative and atherogenic events in non-diabetic hemodialysis (HD) population, are limited. This case-control study was designed to evaluate these parameters in the patients and control subjects and to determine the correlations among the factors. Methods: Forty-nine age- and sex- matched subjects, including 28 non-diabetic HD patients (paired pre-and post-dialysis samples) and 21 control subjects, were enrolled. Ox-LDL and Hcy levels were measured with ELISA and EIA methods, respectively. Arylesterase activity of PON1 was measured by spectrophotometric assay. Results: Compared with the control group, ox-LDL levels were significantly increased both before (p=0.001) and after HD (p=0.036). Arylesterase activity-to-HDL ratio in HD patients was significantly higher than control subjects (p=0.003). Homocysteine levels in the ESRD patients were higher than control subjects both in pre-dialysis and post-dialysis. There was a significant positive correlation (r= 0.25, p= 0.026) between ox-LDL and homocysteine in samples obtained before HD. Logistic regression analysis revealed ox-LDL levels (OR=3.02, p < 0.001) and arylesterase activity/HDL ratio (OR=2.43, p=0.01) to be associated with the increased risk of ESRD. Conclusions: Ox-LDL levels and arylesterase activity/HDL ratio indicated the strongest association with ESRD risk. These factors, especially ox-LDL as an indicator of oxidative stress, may be biomarkers in evaluating the status of non-diabetic ESRD patients. Because of the pathogenic relationship between ox-LDL and homocysteine as nontraditional risk factors of atherosclerosis, therapeutic strategies adopted to reduce them may be useful in decrease of high prevalence of cardiovascular mortality in dialysis patients. In addition, measurement of PON1 activity to HDL ratio is possibly a more valuable biomarker than arylesterase activity alone in non-diabetic ESRD.

scholarly journals Development of Capture Assays for Different Modifications of Human Low-Density Lipoprotein

2005 ◽  
Vol 12 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Gabriel Virella ◽  
M. Brooks Derrick ◽  
Virginia Pate ◽  
Charlyne Chassereau ◽  
Suzanne R. Thorpe ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Gas Chromatography Mass Spectrometry ◽  
Low Density ◽  
Modified Ldl ◽  
Capture Assay ◽  
Carboxymethyl Lysine

ABSTRACT Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL), copper-oxidized LDL (oxLDL), N ε(carboxymethyl) lysine (CML)-modified LDL, and advanced glycosylation end product (AGE)-modified LDL were obtained by immunization of rabbits with in vitro-modified human LDL preparations. After absorption of apolipoprotein B (ApoB) antibodies, we obtained antibodies specific for each modified lipoprotein with unique patterns of reactivity. MDA-LDL antibodies reacted strongly with MDA-LDL and also with oxLDL. CML-LDL antibodies reacted strongly with CML-LDL and also AGE-LDL. oxLDL antibodies reacted with oxLDL but not with MDA-LDL, and AGE-LDL antibodies reacted with AGE-LDL but not with CML-LDL. Capture assays were set with each antiserum, and we tested their ability to capture ApoB-containing lipoproteins isolated from precipitated immune complexes (IC) and from the supernatants remaining after IC precipitation (free lipoproteins). All antibodies captured lipoproteins contained in IC more effectively than free lipoproteins. Analysis of lipoproteins in IC by gas chromatography-mass spectrometry showed that they contained MDA-LDL and CML-LDL in significantly higher concentrations than free lipoproteins. A significant correlation (r = 0.706, P < 0.019) was obtained between the MDA concentrations determined by chemical analysis and by the capture assay of lipoproteins present in IC. In conclusion, we have developed capture assays for different LDL modifications in human ApoB/E lipoprotein-rich fractions isolated from precipitated IC. This approach obviates the interference of IC in previously reported modified LDL assays and allows determination of the degree of modification of LDL with greater accuracy.

Vascular responses and ion exchange in diabetes: Authors' reply

1992 ◽  
Vol 82 (3) ◽  
pp. 339-339
Author(s):  
J. M. Ritter ◽  
G. C. Viberti
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Large Body ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
High Plasma ◽  
Diabetic Patients ◽  
Vascular Sensitivity

1. Na+/Li+ countertransport is not a gold standard, or indeed any other kind of standard. It is a measure of the activity of one particular cation exchanger. 2. There is a large body of literature regarding the effects of oxidized low-density lipoprotein (LDL) in experimental animals and in vitro. Whether abnormal oxidized LDL or one of many other possible mechanisms underlies the inverse relationship that we observed between vascular sensitivity in vivo to nitroprusside or carbachol with erythrocyte Na+/Li+ countertransport in diabetic patients remains to be seen. 3. We caution against post hoc subgroup analysis (smokers versus non-smokers, low versus high plasma lipid levels, etc.) in studies of this size.

Vascular responses and ion exchange in diabetes

1992 ◽  
Vol 82 (3) ◽  
pp. 339-339
Author(s):  
E. N. Wardle
Keyword(s):  
Plasma Level ◽  
Oxidized Ldl ◽  
Saturated Fatty Acids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxides ◽  
Diabetic Patients ◽  
Apparent Relationship ◽  
Long Time ◽  
The Relationship

The use of erythrocyte Na+/Li+ countertransport as a gold standard, as in the article by Halkin et al. (Clin. Sci. 1991; 81, 223–32) [1], should give rise to disquiet because it has been known for a long time that this parameter is influenced by low-density lipoprotein (LDL), by cholesterol and by saturated fatty acids. Recently, it has been clarified that LDL increases the Vmax of this flux [2]. One has to agree that it is interesting that there is an inverse relationship between the ability to dilate blood vessels and Na+/Li+ exchange in the diabetic patient, but actually the basis for this apparent relationship is already known and it is not quite as direct as the authors might wish to imply. It is not native LDL but oxidized LDL [3] that stops the formation of endothelium-derived relaxing factor (EDRF) [4], reduces prostacyclin production and even enhances ‘tissue factor' formation by endothelial cells [5]. In fact, the reduced production of EDRF by diabetic patients that is pertinent to atherogenesis can be correlated with a raised plasma level of cholesterol [6] and also with the plasma level of lipid peroxides [7]. In that case there is some basic information missing concerning the effects of lipid peroxides on Na+/Li+ fluxes in erythrocytes. When this is known, it might well explain why this parameter seems to relate to hypertension and/or nephropathy in diabetic patients. Meantime, in a study of this kind [1] we should have been told which of the subjects were smokers, especially as there were two outstanding points on each graph that formed the relationship.

Gemfibrozil metabolite inhibits in vitro low-density lipoprotein (LDL) oxidation and diminishes cytotoxicity induced by oxidized LDL

Metabolism ◽  
2000 ◽  
Vol 49 (4) ◽  
pp. 479-485 ◽  
Author(s):  
Mitsunobu Kawamura ◽  
Shigeru Miyazaki ◽  
Tamio Teramoto ◽  
Keiko Ashidate ◽  
Hisako Thoda ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Low Density

scholarly journals Oxidized low density lipoprotein inhibits the migration of aortic endothelial cells in vitro.

1993 ◽  
Vol 120 (4) ◽  
pp. 1011-1019 ◽  
Author(s):  
G Murugesan ◽  
G M Chisolm ◽  
P L Fox
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Lipid Hydroperoxide ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Inhibitor Molecule ◽  
Healing Response

Endothelial cell (EC) migration is a critical and initiating event in the formation of new blood vessels and in the repair of injured vessels. Compelling evidence suggests that oxidized low density lipoprotein (LDL) is present in atherosclerotic lesions, but its role in lesion formation has not been defined. We have examined the role of oxidized LDL in regulating the wound-healing response of vascular EC in vitro. Confluent cultures of bovine aortic EC were "wounded" with a razor, and migration was measured after 18 to 24 h as the number of cells moving into the wounded area and the mean distance of cells from the wound edge. Oxidized LDL markedly reduced migration in a concentration- and oxidation-dependent manner. Native LDL or oxidized LDL with a thiobarbituric acid (TBA) reactivity &lt; 5 nmol malondialdehyde equivalents/mg cholesterol was not inhibitory; however, oxidized LDL with a TBA reactivity of 8-12 inhibited migration by 75-100%. Inhibition was half-maximal at 250-300 micrograms cholesterol/ml and nearly complete at 350-400 micrograms/ml. The antimigratory activity was not due to cell death since it was completely reversed 16 h after removal of the lipoprotein. The inhibitor molecule was shown to be a lipid; organic solvent extracts of oxidized LDL inhibited migration to nearly the same extent as the intact particle. When LDL was variably oxidized by dialysis against FeSO4 or CuSO4, or by UV irradiation, the inhibitory activity correlated with TBA reactivity and total lipid peroxides, but not with electrophoretic mobility or fluorescence (360 ex/430 em). This indicates that a lipid hydroperoxide may be the active species. These results suggest the possibility that oxidized LDL may limit the healing response of the endothelium after injury.

scholarly journals Scavenger Receptors Class A-I/II and CD36 Are the Principal Receptors Responsible for the Uptake of Modified Low Density Lipoprotein Leading to Lipid Loading in Macrophages

2002 ◽  
Vol 277 (51) ◽  
pp. 49982-49988 ◽  
Author(s):  
Vidya V. Kunjathoor ◽  
Maria Febbraio ◽  
Eugene A. Podrez ◽  
Kathryn J. Moore ◽  
Lorna Andersson ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Gas Chromatography Mass Spectrometry ◽  
Scavenger Receptors ◽  
Low Density ◽  
Lipid Uptake ◽  
Modified Ldl ◽  
Ldl Uptake

Modification of low density lipoprotein (LDL) can result in the avid uptake of these lipoproteins via a family of macrophage transmembrane proteins referred to as scavenger receptors (SRs). The genetic inactivation of either of two SR family members, SR-A or CD36, has been shown previously to reduce oxidized LDL uptakein vitroand atherosclerotic lesions in mice. Several other SRs are reported to bind modified LDL, but their contribution to macrophage lipid accumulation is uncertain. We generated mice lacking both SR-A and CD36 to determine their combined impact on macrophage lipid uptake and to assess the contribution of other SRs to this process. We show that SR-A and CD36 account for 75–90% of degradation of LDL modified by acetylation or oxidation. Cholesteryl ester derived from modified lipoproteins fails to accumulate in macrophages taken from the double null mice, as assessed by histochemistry and gas chromatography-mass spectrometry. These results demonstrate that SR-A and CD36 are responsible for the preponderance of modified LDL uptake in macrophages and that other scavenger receptors do not compensate for their absence.

scholarly journals Endoplasmic Reticulum Stress Affects Lipid Metabolism in Atherosclerosis Via CHOP Activation and Over-Expression of miR-33

2018 ◽  
Vol 48 (5) ◽  
pp. 1995-2010 ◽  
Author(s):  
Yan Sun ◽  
Dai Zhang ◽  
Xiaoli Liu ◽  
Xuesong Li ◽  
Fang Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Er Stress ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
The Relationship

Background/Aims: Endoplasmic reticulum (ER) stress is an important event in atherosclerosis. Recent studies have shown that ER stress deregulates cholesterol metabolism via multiple pathways. This study aimed to determine the relationship between ER stress and lipid metabolism and to verify that upregulation of miR-33 is involved in this process. Methods: An atherosclerosis model was established in apolipoprotein E-deficient (ApoE-/-) mice fed a Western diet, and THP-1 derived macrophages were used in this study. Hematoxylin-eosin and Oil Red O staining were used to quantify the atherosclerotic plaques. 1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate labeled oxidized low-density lipoprotein binding assay and a Cholesterol Efflux Fluorometric Assay Kit were used to observe cholesterol uptake and efflux. The mRNA and protein levels of biomarkers associated with ER stress and cholesterol metabolism in atherosclerotic plaques and macrophages were evaluated by real-time PCR and western blotting, respectively. Immunofluorescence was used to observe alterations of ABCA1 localization. Small interfering RNAs were used to knock down CHOP and miR-33 in macrophages to alter CHOP and miR-33 expression. Results: Atherosclerotic lesions and systemic lipid levels were ameliorated after inhibition of ER stress (tauroursodeoxycholic acid) in vivo. In vitro studies confirmed that ER stress regulated the lipid catabolism of macrophages by promoting cholesterol uptake, inhibiting cholesterol efflux, and modulating the expression of related transporters. CHOP contributed to lipid metabolism disorder following ER stress. Furthermore, over-expression of miR-33 was involved in ER stress that induced lipid metabolism disorder in macrophages. These findings support a model of ER stress induction by oxidized low-density lipoprotein that affects macrophage lipid catabolism disorder. Conclusion: Our data shed new light on the relationship between ER stress and lipid metabolism in vivo and in vitro, and confirm that upregulation of miR-33 is involved in this process. The relationship between ER stress and miR-33 represents a novel target for the treatment of atherosclerosis.

scholarly journals Lipids from Oxidized Low-Density Lipoprotein Modulate Human Trophoblast Invasion: Involvement of Nuclear Liver X Receptors

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4583-4591 ◽  
Author(s):  
Laëtitia Pavan ◽  
Axelle Hermouet ◽  
Vassilis Tsatsaris ◽  
Patrice Thérond ◽  
Tatsuya Sawamura ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Trophoblast Invasion ◽  
Low Density ◽  
Dependent Manner ◽  
Placental Development ◽  
Concentration Dependent Manner ◽  
Human Trophoblast

Abstract Human embryonic implantation involves major invasion of the uterine wall and remodeling of the uterine arteries by extravillous cytotrophoblast cells (EVCT). Abnormalities in these early steps of placental development lead to poor placentation and fetal growth defects and are frequently associated with preeclampsia, a major complication of human pregnancy. We recently showed that oxidized low-density lipoproteins (oxLDLs) are present in situ in EVCT and inhibit cell invasion in a concentration-dependent manner. The aim of the present study was to better understand the mechanisms by which oxLDL modulate trophoblast invasion. We therefore investigated the presence of oxLDL receptors in our cell culture model of human invasive primary EVCT. We found using immunocytochemistry and immunoblotting that the lectin-like oxLDL receptor-1 was the scavenger receptor mainly expressed in EVCT and was probably involved in oxLDL uptake. We next examined the effect of low-density lipoprotein oxidative state on trophoblast invasion in vitro using EVCT cultured on Matrigel-coated Transwell. We demonstrated that only oxLDL containing a high proportion of oxysterols and phosphatidylcholine hydroperoxide derivatives that provide ligands for liver X receptor (LXR) and peroxisomal proliferator-activated receptor γ (PPARγ), respectively, reduced trophoblast invasion. We next investigated the presence and the role of these nuclear receptors and found that in addition to PPARγ, human invasive trophoblasts express LXRβ, and activation of these nuclear receptors by specific synthetic or natural ligands inhibited trophoblast invasion. Finally, using a PPARγ antagonist, we suggest that LXRβ, rather than PPARγ, is involved in oxLDL-mediated inhibition of human trophoblast invasion in vitro.

scholarly journals Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein

1997 ◽  
Vol 322 (1) ◽  
pp. 317-325 ◽  
Author(s):  
Jesús R. REQUENA ◽  
Min Xin FU ◽  
Mahtab U. AHMED ◽  
Alicia J. JENKINS ◽  
Timothy J. LYONS ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gas Chromatography ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
Low Density ◽  
Lysine Residues

Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(Nε-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(Nε-lysino)propane (LML)] and lysine-HNE [3-(Nε-lysino)-4-hydroxynonan-1-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70Ő80% of total lysine loss during the reaction with MDA. LM and LML (0.002Ő0.12mmol/mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of < 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo.

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