Abstract 1392: Increased High Density Lipoprotein Cholesterol induced by Human Apolipoprotein A-I Gene Transfer increases Adiponectin Expression in abdominal Adipose Tissue

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sophie Van Linthout ◽  
Frank Spillmann ◽  
Anna Foryst-Ludwig ◽  
Carola Bücker-Gärtner ◽  
Marco Meloni ◽  
...  
Keyword(s):  
Gene Transfer ◽  
High Density Lipoprotein ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Dependent Manner ◽  
Human Apolipoprotein ◽  
Protein Levels

Introduction: High density lipoprotein (HDL) cholesterol (C) levels positively correlate with plasma adiponectin levels. However, the role of HDL on adiponectin expression is unkown. To investigate the effect of increased HDL levels on adiponectin expression, 1) gene transfer with human apolipoprotein (apo) A-I, the main apo of HDL, was performed in control mice and in lipopolysaccharide (LPS)-injected mice, associated with decreased adiponectin levels and 2) HDL was supplemented in vitro on (pre)-adipocytes. Methods: Eight weeks old male C57BL/6 mice were i.v. injected with 5 × 10e10 total particles of the E1E3E4-deleted adenoviral vector Ad.hapoA-I, expressing human apo A-I or with the same dose of Ad.Null, containing no expression cassette. Fourteen days hereafter, mice were i.p. injected with LPS from Escherichia coli at a dose of 80 mg/kg or with saline. Mice were sacrificed 12 hours after LPS or saline injection. Human apo A-I and mouse adiponectin plasma concentrations were determined by ELISA. Abdominal fat phospho (p) and total (tot.) Akt protein levels were determined by Western Blot; adiponectin mRNA expression of (pre)-adipocytes by real-time PCR. Results: Ad.hapoA-I GT resulted in human apo A-I expression levels of 83Â27>4.6 mg/dl at day 14, which was associated with 1.8-fold (p<0.05) and 1.5-fold (p<0.05) higher HDL-C and adiponectin levels compared to Ad.Null mice, respectively. After LPS-injection, human apo A-I levels decreased by 1.7-fold (p<0.001), leading to 1.7-fold lower adiponectin levels compared to Ad.hapoA-I control mice, but still 1.5-fold (p<0.01) higher compared to LPS-Ad.Null mice. The increased adiponectin levels in Ad.hapoA-I versus Ad.Null LPS-injected mice were associated with a 1.7-fold (p<0.05) increase in p-Akt/tot.Akt ratio. In vitro, LPS administration decreased adiponectin expression by 2.1-fold (p<0.01), which was normalized to control levels by HDL supplementation in a phosphatidylinositol-3-kinase (PI3K)-dependent manner, since Ly 294002 reversed the HDL-mediated increase in adiponectin expression. Conclusion: HDL increases adiponectin expression via the PI3K-Akt pathway, which may contribute to some of the pleiotropic actions of HDL such as its well-known anti-inflammatory effects.

Libyan family with hypercholesterolemia and increased high-density lipoprotein cholesterol in plasma

1994 ◽  
Vol 40 (12) ◽  
pp. 2313-2316 ◽  
Author(s):  
D S Sheriff ◽  
M el Fakhri ◽  
K Ghwarsha
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Cholesterol Metabolism ◽  
Hepatic Lipase ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Plasma Lipoproteins

Abstract Genetic deficiencies of cholesteryl ester transport protein (CETP) and hepatic lipase activities have been associated with hyperalpha-lipoproteinemias. Here we present a family of 11 members, of which 9, including the father, mother, 5 sons, and 2 daughters, show a marked increase in high-density lipoprotein (HDL) cholesterol alone with low plasma concentrations of triglycerides. Analyses of lecithin:cholesterol acyltransferase (LCAT) activity, cholesteryl ester transfer between HDL fractions, hepatic lipase (HL) activity, and lipoprotein lipase (LPL) activity in these cases showed that a decrease in the heparin-releasable HL activity was the possible cause of the marked increase of HDL2 fractions observed in nine of them. Such a defect in HL activity could significantly affect HDL metabolism in particular and lipoprotein metabolism in general. Evidently, a marked increase in serum total cholesterol due to abnormal metabolism of HDL cholesterol, separate from known causes of altered low-density lipoprotein cholesterol metabolism, e.g., a clearance or a receptor defect, is not uncommon. The coordinated action of HL, LCAT, LPL, and CETP may be essential for normal metabolism of plasma lipoproteins.

scholarly journals High-density lipoprotein metabolism in human apolipoprotein B100transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia

2011 ◽  
Vol 36 (3) ◽  
pp. 313-322 ◽  
Author(s):  
Sarah J. Ehlers ◽  
Stephanie M. Larson ◽  
Heather E. Rasmussen ◽  
Young-Ki Park ◽  
Ji-Young Lee
Keyword(s):  
Adipose Tissue ◽  
High Density Lipoprotein ◽  
Brown Adipose Tissue ◽  
Density Lipoprotein ◽  
High Density ◽  
Type I ◽  
Human Apolipoprotein ◽  
Protein Levels ◽  
Brown Adipose ◽  
Hdl Metabolism

Obese and diabetic humans display decreased plasma high-density lipoprotein cholesterol (HDL-C) concentrations and an increased risk for coronary heart disease. However, investigation on HDL metabolism in obesity with a particular emphasis on hepatic ATP-binding cassette transporter A1 (ABCA1), the primary factor for HDL formation, has not been well studied. Human apolipoprotein B100transgenic (hApoBtg) and brown adipose tissue deficient (BATless) mice were crossed to generate hApoBtg/BATless mice. Male and female hApoBtgand hApoBtg/BATless mice were maintained on either a regular rodent chow diet or a diet high in fat and cholesterol until 24 weeks of age. The hApoBtg/BATless mice that were fed a HF/HC diet became obese, developed hepatic steatosis, and had significantly elevated plasma insulin levels compared with their hApoBtgcounterparts, but plasma concentrations of total cholesterol, HDL-C, triglycerides, and free fatty acids and lipoprotein distribution between genotypes were not significantly different. Hepatic expression of genes encoding HDL-modifying factors (e.g., scavenger receptor, class B, type I, hepatic lipase, lecithin:cholesterol acyltransferase, and phospholipid transfer protein) was either altered significantly or showed a trend of difference between 2 genotypes of mice. Importantly, hepatic protein levels of ABCA1 were significantly lowered by ∼35% in male obese hApoBtg/BATless mice with no difference in mRNA levels compared with hApoBtgcounterparts. Despite reduced hepatic ABCA1 protein levels, plasma HDL-C concentrations were not altered in male obese hApoBtg/BATless mice. The result suggests that hepatic ABCA1 may not be a primary contributing factor for perturbations in HDL metabolism in obesity-induced hyperinsulinemia.

scholarly journals High-Avidity Monoclonal Antibodies against the Human Scavenger Class B Type I Receptor Efficiently Block Hepatitis C Virus Infection in the Presence of High-Density Lipoprotein

2007 ◽  
Vol 81 (15) ◽  
pp. 8063-8071 ◽  
Author(s):  
Maria Teresa Catanese ◽  
Rita Graziani ◽  
Thomas von Hahn ◽  
Martine Moreau ◽  
Thierry Huby ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Dependent Manner ◽  
Class B ◽  
Hcvcc Infection

ABSTRACT The human scavenger class B type 1 receptor (SR-B1/Cla1) was identified as a putative receptor for hepatitis C virus (HCV) because it binds to soluble recombinant HCV envelope glycoprotein E2 (sE2). High-density lipoprotein (HDL), a natural SR-B1 ligand, was shown to increase the in vitro infectivity of retroviral pseudoparticles bearing HCV envelope glycoproteins and of cell culture-derived HCV (HCVcc), suggesting that SR-B1 promotes viral entry in an HDL-dependent manner. To determine whether SR-B1 participates directly in HCV infection or facilitates HCV entry through lipoprotein uptake, we generated a panel of monoclonal antibodies (MAbs) against native human SR-B1. Two of them, 3D5 and C167, bound to conformation-dependent SR-B1 determinants and inhibited the interaction of sE2 with SR-B1. These antibodies efficiently blocked HCVcc infection of Huh-7.5 hepatoma cells in a dose-dependent manner. To examine the role of HDL in SR-B1-mediated HCVcc infection, we set up conditions for HCVcc production and infection in serum-free medium. HCVcc efficiently infected Huh-7.5 cells in the absence of serum lipoproteins, and addition of HDL led to a twofold increase in infectivity. However, the HDL-induced enhancement of infection had no impact on the neutralization potency of MAb C167, despite its ability to inhibit both HDL binding to cells and SR-B1-mediated lipid transfer. Of note, MAb C167 also potently blocked Huh-7.5 infection by an HCV strain recovered from HCVcc-infected chimpanzees. These results demonstrate that SR-B1 is essential for infection with HCV produced in vitro and in vivo and suggest the possible use of anti-SR-B1 antibodies as therapeutic agents.

scholarly journals High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Josefien W. Hommes ◽  
Rachel M. Kratofil ◽  
Sigrid Wahlen ◽  
Carla J. C. de Haas ◽  
Reeni B. Hildebrand ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Bloodstream Infections ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Dependent Manner ◽  
Biological Functions ◽  
Healthy Humans

AbstractStaphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro. We set out to address whether lipoproteins neutralize staphylococcal PSM-associated virulence in experimental animal models. Serum from both LCAT an ABCA1 knockout mice strains which are characterised by near absence of high-density lipoprotein (HDL) levels, was shown to fail to protect against PSM-induced neutrophil activation and lysis in vitro. Importantly, PSM-induced peritonitis in LCAT−/− mice resulted in increased lysis of resident peritoneal macrophages and enhanced neutrophil recruitment into the peritoneal cavity. Notably, LCAT−/− mice were more likely to succumb to staphylococcal bloodstream infections in a PSM-dependent manner. Plasma from homozygous carriers of ABCA1 variants characterized by very low HDL-cholesterol levels, was found to be less protective against PSM-mediated biological functions compared to healthy humans. Therefore, we conclude that lipoproteins present in blood can protect against staphylococcal PSMs, the key virulence factor of community-associated methicillin resistant S. aureus.

scholarly journals High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 574
Author(s):  
Maria Pia Adorni ◽  
Nicoletta Ronda ◽  
Franco Bernini ◽  
Francesca Zimetti
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Current Knowledge ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Current Evidence ◽  
Endocrine Disorders ◽  
Lifestyle Modifications ◽  
Cholesterol Efflux Capacity

Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. The present review describes the current knowledge on HDL CEC modifications in these conditions, focusing on the most recent human studies and on genetic and pathophysiologic aspects. In addition, the most relevant strategies possibly modulating HDL CEC, including lifestyle modifications, as well as nutraceutical and pharmacological interventions, will be discussed. The objective of this review is to help understanding whether, from the current evidence, HDL CEC may be considered as a valid biomarker of CV risk and a potential pharmacological target for novel therapeutic approaches.

Rapid transformation of [3H]cholesteryl ester m rat high-density lipoprotein: in vivo and in vitro studies

Steroids ◽  
1990 ◽  
Vol 55 (7) ◽  
pp. 308-313
Author(s):  
I.J. Goldberg ◽  
R.S. Rosenfeld ◽  
I. Paul ◽  
L.K. Miller ◽  
M.L. Tiell
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Density Lipoprotein ◽  
High Density ◽  
In Vitro Studies ◽  
Rapid Transformation
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