Factor VII Activation, Apolipoprotein A-I and Reverse Cholesterol Transport: Possible Relevance for Postprandial Lipaemia

2002 ◽  
Vol 87 (03) ◽  
pp. 477-482 ◽  
Author(s):  
C. J. Cooke ◽  
M. N. Nanjee ◽  
D. J. Howarth ◽  
J. A. Cooper ◽  
I. P. Stepanova ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Factor Vii ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Cell Surfaces ◽  
Postprandial Lipaemia ◽  
Apolipoprotein A ◽  
Plasma High Density ◽  
Post Infusion ◽  
Significant Activation

SummaryPostprandial lipaemia is associated with activation of factor VII (FVII) and efflux of cholesterol from tissues to nascent plasma high density lipoproteins (HDL) containing apolipoprotein A-I (apo A-I). To determine whether FVII activation and cholesterol efflux occur together in other situations, the responses to intravenous infusion of HDL-like apo A-I/phosphatidylcholine discs were measured in 10 healthy men. Disc infusion (40 mg apo A-I/kg body weight) over 4 h was followed by increases in HDL cholesteryl ester and plasma apo A-I (p <0.0001). Significant activation of FVII was apparent during infusion in fasting subjects (p = 0.03), activated FVII averaging 123% of baseline value by 12 h (p <0.0001). Plasma thrombin-antithrombin (TAT) complex increased to 156% of baseline level by 12 h (p >0.05) but individual responses differed considerably. Peak TAT post-infusion was associated inversely with peak HDL triglyceride concentration (p = 0.004). The coagulation responses to disc-infusion may be due to transfer of phosphatidylserine to cell surfaces during cholesterol efflux.

Apolipoprotein A-I stimulates the transport of intracellular cholesterol to cell-surface cholesterol-rich domains (caveolae)

2001 ◽  
Vol 358 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Dmitri SVIRIDOV ◽  
Noel FIDGE ◽  
Gabrielle BEAUMIER-GALLON ◽  
Christopher FIELDING
Keyword(s):  
Cell Surface ◽  
Cholesterol Efflux ◽  
Partial Purification ◽  
Cholesterol Transport ◽  
Dependent Manner ◽  
Cholesterol Trafficking ◽  
Apolipoprotein A ◽  
Intracellular Cholesterol ◽  
Plasma Apolipoprotein ◽  
Stimulation Of

We have studied the effect of lipid-free human plasma apolipoprotein A-I (apoA-I) on the transport of newly synthesized cholesterol to cell-surface cholesterol-rich domains, which in human skin fibroblasts are mainly represented by caveolae. Changes in transport of newly synthesized cholesterol were assessed after labelling cells with [14C]acetate at 15°C and warming cells to permit the transfer of cholesterol, followed by the selective oxidation of cholesterol in cholesterol-rich domains (caveolae) in the plasma membrane before their partial purification. ApoA-I, but not BSA added in an equimolar concentration, enhanced the transport of cholesterol to the caveolae up to 5-fold in a dose- and time-dependent manner. The effect of apoA-I on cholesterol transport exceeded its effect on cholesterol efflux, resulting in an accumulation of intracellular cholesterol in caveolae. Methyl-β-cyclodextrin, added at a concentration promoting cholesterol efflux to the same extent as apoA-I, also stimulated cholesterol trafficking, but was 3-fold less effective than apoA-I. Progesterone inhibited the transport of newly synthesized cholesterol to the caveolae. Treatment of cells with apoA-I stimulated the expression of caveolin, increasing the amount of caveolin protein and mRNA by approx. 2-fold. We conclude that apoA-I induces the transport of intracellular cholesterol to cell-surface caveolae, possibly in part through the stimulation of caveolin expression.

Abstract 631: Lipid Composition of Gold Nanoparticle-Templated High-Density Lipoprotein Analogs Dictates Cholesterol Efflux Function

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
R Kannan Mutharasan ◽  
Amritha T Singh ◽  
Kaylin M McMahon ◽  
C Shad Thaxton
Keyword(s):  
Fatty Acid ◽  
Lipid Content ◽  
Lipid Composition ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Lipid Membrane ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Cholesterol Transport

Background: Reverse cholesterol transport, the process by which cholesterol is effluxed from cells to high-density lipoproteins (HDL) and is delivered to the liver for clearance, is a promising pathway to augment for treatment of atherosclerosis. Though structure-function relationships for nascent, discoidal HDL and cholesterol efflux have been well studied, how the lipid composition of spherical HDL species - which varies in pathophysiological conditions - impacts their ability to mediate cholesterol efflux has not been investigated. Methods and Results: Spherical gold nanoparticles (5 nm) were used to synthesize spherical HDL analogs (HDL-NP) by adding ApoAI protein, and various lipids. With this strategy a panel of HDL-NP varying in lipid content was generated. HDL-NP designs tested include: dipalmitylphosphatidylcholine (DPPC, saturated fatty acid), dioleoylphosphatidylcholine (DOPC, unsaturated fatty acid), sphingomyelin, lysophosphatidylcholine (LPC), and mixtures thereof. All of these species are found in natural HDL. After characterizing protein and lipid stoichiometry of the purified HDL-NP, these HDL-NP designs were tested in the cellular reverse cholesterol transport assay using J774 mouse macrophages. These studies demonstrate that all HDL-NP designs mediate more efflux than equimolar amounts of ApoAI protein control, and further demonstrate that HDL-NP designs incorporating unsaturated phospholipid (DOPC), sphingomyelin, and LPC - each of which can increase disorder in the lipid membrane and thus give rise to opportunity for cholesterol to intercalate and bind - enhance cholesterol efflux compared to saturated phospholipid (DPPC) design. Conclusion: In summary, these results demonstrate that lipid content of HDL-NP - analogs of spherical HDL - dictates cholesterol efflux function, a finding which sheds light on the functional importance of lipid content variation seen in mature, spherical HDL species.

Cell Cholesterol Efflux to Reconstituted High-Density Lipoproteins Containing the Apolipoprotein A-IMilanoDimer

Biochemistry ◽  
1999 ◽  
Vol 38 (49) ◽  
pp. 16307-16314 ◽  
Author(s):  
Laura Calabresi ◽  
Monica Canavesi ◽  
Franco Bernini ◽  
Guido Franceschini
Keyword(s):  
Cholesterol Efflux ◽  
High Density ◽  
High Density Lipoproteins ◽  
Apolipoprotein A

scholarly journals HDL mediates reverse cholesterol transport from ram spermatozoa and induces hyperactivated motility

2021 ◽  
Author(s):  
Naomi C Bernecic ◽  
Simon P Graaf ◽  
Tamara Leahy ◽  
Bart M Gadella
Keyword(s):  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Scavenger Receptor ◽  
High Density Lipoproteins ◽  
In Vitro Fertilisation ◽  
Critical Event ◽  
Cholesterol Transport ◽  
Type I

ABSTRACT Reverse Cholesterol Transport or cholesterol efflux is part of an extensive plasma membrane remodelling process in spermatozoa that is imperative for fertilisation. For ram spermatozoa, sheep serum is well known to support in vitro fertilisation (IVF), but knowledge of its explicit role is limited. Though, it is postulated to elicit cholesterol efflux owing to the presence of high density lipoproteins (HDLs) that interact with transmembrane cholesterol transporters, such as ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B, type I (SR-BI). In this study, we report that both sheep serum and HDLs were able to elicit cholesterol efflux alone by up to 20–40% (as measured by the BODIPY-cholesterol assay). Furthermore, when the antagonists glibenclamide and valspodar were used to inhibit the function of ABCA1 and SR-BI or ABCA1 alone, respectively, cholesterol efflux was only marginally reduced (8–15)%. Nevertheless, it is likely that in ram spermatozoa, a specific facilitated pathway of cholesterol efflux is involved in the interaction between cholesterol acceptors and transporters. Interestingly, exposure to HDLs also induced hyperactivated motility, another critical event required for successful fertilisation. Taken together, this study details the first report of the dual action of HDLs on ram spermatozoa, providing both an insight into the intricacy of events leading up to fertilisation in vivo as well as demonstrating the possible application of HDL supplementation in media for IVF.

scholarly journals Anti-apolipoprotein A-1 autoantibodies correlate with disease activity in systemic lupus erythematosus

Rheumatology ◽  
2019 ◽  
Author(s):  
Haïg Nigolian ◽  
Camillo Ribi ◽  
Delphine S Courvoisier ◽  
Sabrina Pagano ◽  
Montserrat Alvarez ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Reverse Cholesterol Transport ◽  
Clinical Performance ◽  
Antioxidant Properties ◽  
Cross Reactivity ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Apolipoprotein A ◽  
Laboratory Markers

Abstract Objectives Apolipoprotein A-1 (ApoA-1) is a protein fraction of the high-density lipoproteins with anti-inflammatory and antioxidant properties that play a major role in reverse cholesterol transport. The presence of anti-ApoA-1 IgG has been reported in SLE to be variably associated with disease activity or cardiovascular events (CVEs). We assessed the clinical performance of anti-ApoA-1 IgG and of antibodies directed against its immunodominant F3L1 peptide (F3L1 IgG) in a well-characterized Swiss SLE cohort study. Methods A total of 354 biological samples and interviews from 176 individuals were studied. SLEDAI, clinical characteristics, anamnestic CVEs and therapy details were recorded. Sera were tested for the presence of anti-ApoA-1 IgG, anti-F3L1 IgG, anti-dsDNA IgG and aPL. Results Anti-ApoA-1 and anti-F3L1 IgG positivity was associated with higher SLEDAI, mostly due to concomitant positivity of dsDNA IgG and low complement. Variations in time of anti-ApoA-1 IgG correlated positively with variations of anti-dsDNA IgG and inversely to variations of C3 levels. No cross-reactivity was found between anti-ApoA-1 and anti-dsDNA IgG. Positivity for anti-Apo-A1 IgG was more frequent in individuals receiving 10 mg/day or more of prednisone. We did not find any significant association between anti-ApoA-1 IgG positivity and CVEs. Conclusion Anti-ApoA-1 and anti-F3L1 IgG in SLE correlate strongly with laboratory markers of activity, particularly with the presence and titre of dsDNA IgG. These results confirm and extend previous findings and support the use of anti-ApoA1 IgG in the clinical setting. Their role in CVEs deserves further investigation.

scholarly journals A short peptide of the C-terminal class Y helices of apolipoprotein A-I has preserved functions in cholesterol efflux and in vivo metabolic control

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shelley J. Edmunds ◽  
Rebeca Liébana-García ◽  
Karin G. Stenkula ◽  
Jens O. Lagerstedt
Keyword(s):  
Metabolic Control ◽  
Glucose Control ◽  
Cholesterol Efflux ◽  
Cholesterol Transport ◽  
Resistant Mouse ◽  
Short Peptide ◽  
Insulin Resistant ◽  
Apolipoprotein A ◽  
The Impact

Abstract Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) induces glucose uptake by muscle tissues and stimulates pancreatic insulin secretion, and also facilitates cholesterol transport in circulation, and is explored for anti-diabetic and anti-atherosclerotic treatments. As the better alternative to complex protein–lipid formulations it was recently established that the C-terminal region of the ApoA-I protein singly improves the metabolic control and prevents formation of atherosclerotic plaques. Additional investigations of peptides based on the ApoA-I structure may lead to novel anti-diabetic drugs. We here investigate a short peptide (33mer, RG33) that corresponds to the two last helical segments (aa 209–241) of the ApoA-I structure (so-called class Y-helices which forms amphipathic helices) for stability and solubility in serum, for in vitro cholesterol efflux capability, and for providing in vivo glucose control in an insulin resistant mouse model. The RG33 peptide efficiently solubilizes lipid-vesicles, and promotes the efflux of cholesterol from cultured macrophages. The efflux capacity is significantly increased in the presence of lipids compared to non-lipidated RG33. Finally, acute treatment with the RG33 peptide significantly improves the glucose clearance capacity of insulin resistant mice. The impact of the RG33 peptide on glucose control and cholesterol transport, as well as the physicochemical properties, makes it a good candidate for translational exploration of its therapeutic potential in diabetes treatment.

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