scholarly journals Oxidation of high-density lipoprotein HDL3 leads to exposure of apo-AI and apo-AII epitopes and to formation of aldehyde protein adducts, and influences binding of oxidized low-density lipoprotein to type I and type III collagen in vitro1

1998 ◽  
Vol 331 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Joachim GREILBERGER ◽  
Günther JÜRGENS
Keyword(s):  
High Density Lipoprotein ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protein Adducts ◽  
Type I ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Immunological Properties ◽  
Apo Ai

The changes in the immunological properties of apolipoprotein AI (apo-AI) and AII (apo-AII) during the oxidation of the high-density lipoprotein HDL3 and its influence on the binding of heavily oxidized low-density lipoprotein (LDL) to type I and III collagen were investigated. Oxidation of HDL3 or Eu3+-labelled HDL3 was performed with CuSO4, varying the time of oxidation. Oxidation of HDL3 resulted in an increase in lipid hydroperoxides and enhanced the negative charge of this lipoprotein. Immunological studies with a solid-phase sandwich immunoassay revealed a strong increase in binding of Eu3+-labelled HDL3 to polyclonal antibodies against apo-AI and apo-AII within the first 4 h of oxidation. Neo-epitopes were also formed by interaction of the apolipoproteins with degradation products from the lipid peroxidation of polyunsaturated fatty acids, as evidenced by an immunoreaction of oxidized Eu3+-labelled HDL3 with antibodies to 4-hydroxynonenal (4-HNE)– and malondialdehyde (MDA)–protein adducts. Western blot analysis of oxidized HDL3 samples showed, as well as apo-AI and apo-AII bands, larger aggregated apolipoproteins, occurring after 0.5–2.5 h of oxidation. These aggregates were recognized by antibodies to apo-AI and apo-AII as well as by antibodies to 4-HNE- and MDA-protein adducts. Furthermore the original apo-AI monomers and apo-AII dimers decreased during the oxidation. The ability of native and oxidized HDL3 to prevent the binding of Eu3+-labelled 24 h-oxidized LDL to collagen on microtitration plates was estimated. Interestingly, 2 h-oxidized HDL3 competed most with the binding of 24 h-oxidized LDL on collagen type I and type III, followed by native HDL3. However, 24 h-oxidized HDL3 was a weaker competitor. Thus oxidative modification of HDL3 strongly alters the immunological properties of this lipoprotein and its binding affinity for collagen.

scholarly journals Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3

2000 ◽  
Vol 41 (9) ◽  
pp. 1495-1508 ◽  
Author(s):  
Mohamad Navab ◽  
Susan Y. Hama ◽  
G.M. Anantharamaiah ◽  
Kholood Hassan ◽  
Greg P. Hough ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein

Oxidative stress augments pulmonary hypertension in chronically hypoxic mice overexpressing the oxidized LDL receptor

2013 ◽  
Vol 305 (2) ◽  
pp. H155-H162 ◽  
Author(s):  
Sayoko Ogura ◽  
Tatsuo Shimosawa ◽  
ShengYu Mu ◽  
Takashi Sonobe ◽  
Fumiko Kawakami-Mori ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ros Generation ◽  
Low Density ◽  
Ros Production ◽  
Oxidized Low Density Lipoprotein

Chronic hypoxia is one of the main causes of pulmonary hypertension (PH) associated with ROS production. Lectin-like oxidized low-density lipoprotein receptor (LOX)-1 is known to be an endothelial receptor of oxidized low-density lipoprotein, which is assumed to play a role in the initiation of ROS generation. We investigated the role of LOX-1 and ROS generation in PH and vascular remodeling in LOX-1 transgenic (TG) mice. We maintained 8- to 10-wk-old male LOX-1 TG mice and wild-type (WT) mice in normoxia (room air) or hypoxia (10% O2 chambers) for 3 wk. Right ventricular (RV) systolic pressure (RVSP) was comparable between the two groups under normoxic conditions; however, chronic hypoxia significantly increased RVSP and RV hypertrophy in LOX-1 TG mice compared with WT mice. Medial wall thickness of the pulmonary arteries was significantly greater in LOX-1 TG mice than in WT mice. Furthermore, hypoxia enhanced ROS production and nitrotyrosine expression in LOX-1 TG mice, supporting the observed pathological changes. Administration of the NADPH oxidase inhibitor apocynin caused a significant reduction in PH and vascular remodeling in LOX-1 TG mice. Our results suggest that LOX-1-ROS generation induces the development and progression of PH.

Influence of gender on vasomotor effects of oxidized low-density lipoprotein in porcine coronary arteries

1997 ◽  
Vol 272 (6) ◽  
pp. H2577-H2583 ◽  
Author(s):  
D. A. Cox ◽  
M. L. Cohen
Keyword(s):  
Coronary Arteries ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Male And Female ◽  
No Release ◽  
Contraction And Relaxation ◽  
Coronary Endothelium

This study compared 5-hydroxytryptamine (5-HT)-induced contraction and relaxation in coronary arteries from male and female pigs and compared the vasomotor effects of the atherosclerotic lipoprotein, oxidized low-density lipoprotein (LDL), in these tissues. 5-HT-induced contraction and endothelium-dependent relaxation were similar, as was sodium nitroprusside-induced relaxation, in coronary arteries from male and female pigs. These data suggest that there were no gender-related differences in 5-HT-induced contraction or 5-HT-mediated nitric oxide (NO) release from the coronary endothelium. In contrast, oxidized LDL (100 micrograms/ml) enhanced 5-HT-induced contraction to a greater extent in coronary arteries from male versus female pigs. Because oxidized LDL inhibited 5-HT-induced relaxation similarly in arteries from male and female animals, a greater effect of oxidized LDL on agonist-induced NO release in tissues from male pigs cannot explain the greater effect on 5-HT-induced contraction. Oxidized LDL contracted coronary arteries from males with a greater force than arteries from females when measured from baseline tone, suggesting that oxidized LDL inhibited basal NO release to a greater extent in coronary arteries from male pigs compared with females, an effect that may have participated in the greater enhancement of 5-HT-induced contraction that occurred in arteries from male pigs. These gender-related differences in the vasomotor effects of oxidized LDL may play an important role in the lesser incidence of cardiovascular disease in premenopausal females than in males and may provide insight into the cardioprotective effect of estrogen.

scholarly journals Treatment of macrophages with oxidized low-density lipoprotein increases their intracellular glutathione content

1991 ◽  
Vol 278 (2) ◽  
pp. 429-434 ◽  
Author(s):  
V M Darley-Usmar ◽  
A Severn ◽  
V J O'Leary ◽  
M Rogers
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Monocyte ◽  
Cell Types ◽  
Oxidative Modification ◽  
Glutathione Depletion ◽  
Lipid Phase ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein

Macrophages derived from the human monocyte cell line THP-1 or isolated from the peritoneum of C3H/HEJ mice were incubated with oxidized low-density lipoprotein (LDL) and the total glutathione content (oxidized plus reduced) was measured. An initial depletion of glutathione was followed by an increase, such that after a period of 24 h the glutathione content has approximately doubled. This response required the oxidation of the lipid phase of the LDL molecule, since both native LDL and acetylated LDL had little effect on glutathione levels. The response of the cells to oxidized LDL was dependent on the extent of oxidative modification of the protein. It was also found that 4-hydroxynonenal had a similar effect on THP-1 cells, and we suggest that this or other aldehydes present in oxidized LDL causes the induction of glutathione synthesis in response to an initial oxidative stress and consequent glutathione depletion. In addition, we found that both cell types possess transferases and peroxidases capable of detoxifying aldehydes and peroxides. However, treatment of cells with oxidized LDL or 4-hydroxynonenal for a period of 24 h had no effect on the activities of these enzymes.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1): a crucial driver of atherosclerotic cardiovascular disease

2020 ◽  
Author(s):  
Alexander Akhmedov ◽  
Tatsuya Sawamura ◽  
Chu-Huang Chen ◽  
Simon Kraler ◽  
Daria Vdovenko ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Basic Research ◽  
Plaque Formation ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Atheromatous Plaques

Abstract Cardiovascular diseases (CVDs), specifically lipid-driven atherosclerotic CVDs, remain the number one cause of death worldwide. The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a scavenger receptor that promotes endothelial dysfunction by inducing pro-atherogenic signalling and plaque formation via the endothelial uptake of oxidized LDL (oxLDL) and electronegative LDL, contributes to the initiation, progression, and destabilization of atheromatous plaques, eventually leading to the development of myocardial infarction and certain forms of stroke. In addition to its expression in endothelial cells, LOX-1 is expressed in macrophages, cardiomyocytes, fibroblasts, dendritic cells, lymphocytes, and neutrophils, further implicating this receptor in multiple aspects of atherosclerotic plaque formation. LOX-1 holds promise as a novel diagnostic and therapeutic target for certain CVDs; therefore, understanding the molecular structure and function of LOX-1 is of critical importance. In this review, we highlight the latest scientific findings related to LOX-1, its ligands, and their roles in the broad spectrum of CVDs. We describe recent findings from basic research, delineate their translational value, and discuss the potential of LOX-1 as a novel target for the prevention, diagnosis, and treatment of related CVDs.

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