scholarly journals Immune Response to Lipoproteins in Atherosclerosis

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sonia Samson ◽  
Lakshmi Mundkur ◽  
Vijay V. Kakkar
Keyword(s):  
Immune Response ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Adaptive Immune System ◽  
Low Density ◽  
Novel Therapy ◽  
Self Tolerance ◽  
Elevated Serum Cholesterol

Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

Influence of Etoposide on the Retention of Radiolabeled Low-Density Lipoprotein in the Arterial Wall

1999 ◽  
Vol 123 (6) ◽  
pp. 514-518
Author(s):  
Michael Krainer ◽  
Margarida Rodrigues ◽  
Christoph Zielinski ◽  
Helmut Sinzinger
Keyword(s):  
Testicular Cancer ◽  
Serum Cholesterol ◽  
Arterial Wall ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Low Density ◽  
Etoposide Treatment ◽  
Elevated Serum Cholesterol

Abstract Background.—Cardiovascular toxicity of chemotherapy for testicular cancer is a matter of discussion, since highly efficient agents can achieve cure of the disease, even in the metastasized setting. Acute ischemic events during the treatment period and a persistently elevated serum cholesterol thereafter are observations of particular concern in these patients, and the underlying basic mechanisms are unknown to date. Objective.—To evaluate etoposide, which is part of the standard treatment for testicular cancer, as a potential cause of atherogenesis in an experimental model. Setting.—Aortic 125I-labeled low-density lipoprotein retention was studied in 72 cholesterol-fed rabbits under etoposide treatment and was quantified according to the morphologically assessed type of surface lining. Aortic cholesterol content was determined both by Sudan III staining and quantitatively by a biochemical assay. Results.—A reduced uptake of 125I-labeled low-density lipoprotein in the arterial wall was observed in the etoposide-treated animals, which resulted in a size reduction of sudanophilic areas and cholesterol content. Whereas the breakdown of 125I-labeled low-density lipoprotein in the liver was not significantly enhanced, the plasma decay of 125I-labeled low-density lipoprotein was faster and serum cholesterol was lower in the etoposide group than in controls. Conclusion.—Unexpectedly, we found an improvement of arterial wall lipid metabolism under etoposide treatment and can thus exclude this substance as a promoter of atherogenesis in this model.

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.

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.

scholarly journals Plasma exosome-derived microRNAs expression profiling and bioinformatics analysis under cross-talk between increased low-density lipoprotein cholesterol level and ATP-sensitive potassium channels variant rs1799858

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Cheng Liu ◽  
Yanxian Lai ◽  
Songsong Ying ◽  
Junfang Zhan ◽  
Yan Shen
Keyword(s):  
Potassium Channels ◽  
Expression Profile ◽  
Cross Talk ◽  
Target Genes ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Background Exosome-derived microRNAs (exo-miRs) as messengers play important roles, in the cross-talk between genetic [ATP-sensitive potassium channels (KATP) genetic variant rs1799858] and environmental [elevated serum low-density lipoprotein cholesterol (LDL-C) level] factors, but the plasma exo-miRs expression profile and its role in biological processes from genotype to phenotype remain unclear. Methods A total of 14 subjects with increased LDL-C serum levels (≥ 1.8 mmol/L) were enrolled in the study. The KATP rs1799858 was genotyped by the Sequenom MassARRAY system. The plasma exo-miRs expression profile was identified by next-generation sequencing. Results 64 exo-miRs were significantly differentially expressed (DE), among which 44 exo-miRs were up-regulated and 20 exo-miRs were down-regulated in those subjects carrying T-allele (TT + CT) of rs1799858 compared to those carrying CC genotype. The top 20 up-regulated DE-exo-miRs were miR-378 family, miR-320 family, miR-208 family, miR-483-5p, miR-22-3p, miR-490-3p, miR-6515-5p, miR-31-5p, miR-210-3p, miR-17-3p, miR-6807-5p, miR-497-5p, miR-33a-5p, miR-3611 and miR-126-5p. The top 20 down-regulated DE-exo-miRs were let-7 family, miR-221/222 family, miR-619-5p, miR-6780a-5p, miR-641, miR-200a-5p, miR-581, miR-605-3p, miR-548ar-3p, miR-135a-3p, miR-451b, miR-509-3-5p, miR-4664-3p and miR-224-5p. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently implemented to identify the top 10 DE-exo-miRs related specific target genes and signaling pathways. Only 5 DE-exo-miRs were validated by qRT-PCR as follows: miR-31-5p, miR-378d, miR-619-5p, miR-320a-3p and let-7a-5p (all P < 0.05). Conclusion These results firstly indicated the plasma exo-miRs expression profile bridging the link between genotype (KATP rs1799858) and phenotype (higher LDL-C serum level), these 5 DE-exo-miRs may be potential target intermediates for molecular intervention points.

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.

ELEVATED SERUM LOW DENSITY LIPOPROTEIN (LDL) IS ASSOCIATED WITH AN INCREASED RISK OF PROSTATE CANCER IN AFRICAN-AMERICAN MEN

2008 ◽  
Vol 179 (4S) ◽  
pp. 150-150
Author(s):  
Kelvin A Moses ◽  
Thura T Abd ◽  
John A Hall ◽  
Michael Goodman ◽  
Muta M Issa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African American Men ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Low Density ◽  
Increased Risk

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.

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