scholarly journals In vivo evidence for reduced binding of low density lipoproteins to receptors as a cause of primary moderate hypercholesterolemia.

1986 ◽  
Vol 78 (5) ◽  
pp. 1410-1414 ◽  
Author(s):  
G L Vega ◽  
S M Grundy
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density

Effects of oxidized low-density lipoproteins on the hepatic microvasculature

2011 ◽  
Vol 301 (4) ◽  
pp. G684-G693 ◽  
Author(s):  
Ana Oteiza ◽  
Ruomei Li ◽  
Robert S. McCuskey ◽  
Bård Smedsrød ◽  
Karen Kristine Sørensen
Keyword(s):  
Electron Microscopy ◽  
Linear Trend ◽  
Density Lipoprotein ◽  
Low Density Lipoproteins ◽  
Intercellular Adhesion Molecule ◽  
Organ Distribution ◽  
Low Density ◽  
Hepatic Microcirculation ◽  
Oxidized Low Density Lipoproteins

Oxidized low-density lipoproteins (oxLDLs) are involved in proinflammatory and cytotoxic events in different microcirculatory systems. The liver is an important scavenger organ for circulating oxLDLs. However, the interaction of oxLDL with the hepatic microcirculation has been poorly investigated. The present study was conducted to examine the effects of differently modified oxLDLs on the hepatic microvasculature. C57Bl/6J mice were injected intravenously with low-density lipoprotein (LDL), or LDL oxidized for 3 h (oxLDL3) or 24 h (oxLDL24), at doses resembling oxLDL plasma levels in cardiovascular disease patients. Radioiodinated ligands were used to measure blood decay and organ distribution, and nonlabeled ligands to evaluate microcirculatory responses, examined by in vivo microscopy 30–60 min after ligand injection, immunohistochemistry, and scanning and transmission electron microscopy. Mildly oxLDL (oxLDL3) was cleared from blood at a markedly slower rate than heavily oxLDL (oxLDL24), but significantly faster than LDL ( P < 0.01). Injected oxLDLs distributed to liver. OxLDL effects were most pronounced in central areas of the liver lobules where oxLDL3elicited a significant ( P < 0.05) reduction in perfused sinusoids, and both oxLDL3and oxLDL24significantly increased the numbers of swollen endothelial cells and adherent leukocytes compared with LDL ( P < 0.05). OxLDL-treated livers also exhibited increased intercellular adhesion molecule (ICAM)-1 centrilobular staining. Electron microscopy showed a 30% increased thickness of the liver sinusoidal endothelium in the oxLDL3group ( P < 0.05) and a reduced sinusoidal fenestration in centrilobular areas with increased oxidation of LDL ( P for linear trend <0.05). In conclusion, OxLDL induced several acute changes in the liver microvasculature, which may lead to sinusoidal endothelial dysfunction.

scholarly journals Antioxidant and Protective Effects of Artemisia campestris Essential Oil Against Chlorpyrifos-Induced Kidney and Liver Injuries in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Mongi Saoudi ◽  
Riadh Badraoui ◽  
Fatma Rahmouni ◽  
Kamel Jamoussi ◽  
Abdelfattah El Feki
Keyword(s):  
Essential Oil ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Protective Effects ◽  
Liver Injuries ◽  
Liver And Kidney ◽  
Artemisia Campestris ◽  
Morphologic Changes ◽  
Histopathologic Features

This study is aimed to elucidate the possible antioxidant and protective effects of Artemisia campestris essential oil (ACEO) against the deleterious effects of chlorpyrifos (CPF) in rats. The in vivo study revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activities and the serum contents of creatinine, urea, uric acid, cholesterol, triglycerides, low density lipoproteins (LDL), and glucose in rats treated with CPF as compared to controls. Meanwhile, hepatic and renal activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver and kidney decreased and the content of malondialdehyde (MDA) increased. Some histopathologic features were noticed in liver and kidney of the CPF group. Interestingly, ACEO alleviated the biochemical disruptions and reduced these hepato-renal morphologic changes.

scholarly journals Macrophages Create an Acidic Extracellular Hydrolytic Compartment to Digest Aggregated Lipoproteins

2009 ◽  
Vol 20 (23) ◽  
pp. 4932-4940 ◽  
Author(s):  
Abigail S. Haka ◽  
Inna Grosheva ◽  
Ethan Chiang ◽  
Adina R. Buxbaum ◽  
Barbara A. Baird ◽  
...  
Keyword(s):  
Free Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoproteins ◽  
Critical Event ◽  
Low Density ◽  
Acid Hydrolases ◽  
Detailed Understanding ◽  
Physical Features

A critical event in atherogenesis is the interaction of macrophages with subendothelial lipoproteins. Although most studies model this interaction by incubating macrophages with monomeric lipoproteins, macrophages in vivo encounter lipoproteins that are aggregated. The physical features of the lipoproteins require distinctive mechanisms for their uptake. We show that macrophages create an extracellular, acidic, hydrolytic compartment to carry out digestion of aggregated low-density lipoproteins. We demonstrate delivery of lysosomal contents to these specialized compartments and their acidification by vacuolar ATPase, enabling aggregate catabolism by lysosomal acid hydrolases. We observe transient sealing of portions of the compartments, allowing formation of an “extracellular” proton gradient. An increase in free cholesterol is observed in aggregates contained in these compartments. Thus, cholesteryl ester hydrolysis can occur extracellularly in a specialized compartment, a lysosomal synapse, during the interaction of macrophages with aggregated low-density lipoprotein. A detailed understanding of these processes is essential for developing strategies to prevent atherosclerosis.

scholarly journals Aggregation and fusion of low-density lipoproteins in vivo and in vitro

2013 ◽  
Vol 4 (5) ◽  
pp. 501-518 ◽  
Author(s):  
Mengxiao Lu ◽  
Olga Gursky
Keyword(s):  
Lipid Droplet ◽  
Current Knowledge ◽  
Single Copy ◽  
Droplet Formation ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Atherosclerotic Lesions ◽  
Lipid Droplet Formation

AbstractLow-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions.

Probucol protects low-density lipoproteins from in vitro and in vivo oxidation

1994 ◽  
Vol 29 (4) ◽  
pp. 337-344 ◽  
Author(s):  
Gabriele Bittolo-Bon ◽  
Giuseppe Cazzolato ◽  
Pietro Avogaro
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density

Extracorporeal Enzymatic Removal of Low Density Lipoproteins in Rabbits: Efficacy and Safety

1993 ◽  
Vol 16 (4) ◽  
pp. 218-228 ◽  
Author(s):  
S.D. Shefer ◽  
J. Ferreira ◽  
C. J-P. Mullon ◽  
R. Langer
Keyword(s):  
New Zealand ◽  
Plasma Cholesterol ◽  
Low Density Lipoproteins ◽  
The Body ◽  
Cholesterol Concentration ◽  
Enzyme Assays ◽  
Low Density ◽  
Plasma Cholesterol Concentration ◽  
New Zealand White Rabbits

An extracorporeal circuit incorporating a plasma separator reactor (PSR) was designed to modify low density lipoproteins (LDL). The PSR was tested in vivo with hypercholesterolemic New Zealand White rabbits. The bioreactor enzymatically converts LDL to a form that can be removed by the body at an enhanced rate. The physiological response of hypercholesterolemic New Zealand White rabbits to 90 minute extracorporeal treatments was monitored. The total plasma cholesterol concentration in the treated rabbits fell sharply (up to 40% decrease) during and following the treatment. Results of safety tests indicate no significant enzyme leaching from the device, no disruption or damage to erythrocytes, no increase in white blood cell count and no liver damage as indicated by five enzyme assays. All safety measurements suggest that the treatment is safe.

Acute Exposure of Collecting Lymphatic Vessels to Low-Density Lipoproteins Increases Both Contraction Frequency and Lymph Flow: An In Vivo Mechanical Insight

2020 ◽  
Vol 18 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Eleonora Solari ◽  
Cristiana Marcozzi ◽  
Barbara Bartolini ◽  
Manuela Viola ◽  
Daniela Negrini ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Low Density Lipoproteins ◽  
Lymph Flow ◽  
Acute Exposure ◽  
Low Density ◽  
Contraction Frequency
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