scholarly journals High-Density Lipoproteins as Homeostatic Nanoparticles of Blood Plasma

2020 ◽  
Vol 21 (22) ◽  
pp. 8737
Author(s):  
Vasily A. Kudinov ◽  
Olga Yu. Alekseeva ◽  
Tatiana I. Torkhovskaya ◽  
Konstantin K. Baskaev ◽  
Rafael I. Artyushev ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Antioxidant Properties ◽  
High Density ◽  
Point Of View ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Intercellular Signaling ◽  
Peripheral Tissues ◽  
Inflammatory Processes ◽  
Living Organisms

It is well known that blood lipoproteins (LPs) are multimolecular complexes of lipids and proteins that play a crucial role in lipid transport. High-density lipoproteins (HDL) are a class of blood plasma LPs that mediate reverse cholesterol transport (RCT)—cholesterol transport from the peripheral tissues to the liver. Due to this ability to promote cholesterol uptake from cell membranes, HDL possess antiatherogenic properties. This function was first observed at the end of the 1970s to the beginning of the 1980s, resulting in high interest in this class of LPs. It was shown that HDL are the prevalent class of LPs in several types of living organisms (from fishes to monkeys) with high resistance to atherosclerosis and cardiovascular disorders. Lately, understanding of the mechanisms of the antiatherogenic properties of HDL has significantly expanded. Besides the contribution to RCT, HDL have been shown to modulate inflammatory processes, blood clotting, and vasomotor responses. These particles also possess antioxidant properties and contribute to immune reactions and intercellular signaling. Herein, we review data on the structure and mechanisms of the pleiotropic biological functions of HDL from the point of view of their evolutionary role and complex dynamic nature.

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.

Abstract 404: Altered Interaction of Modified High Density Lipoprotein with Scavenger Receptor BI

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Alexandra C Chadwick ◽  
Rebecca L Holme ◽  
Paula-Dene C Nesbeth ◽  
Kirkwood A Pritchard ◽  
Daisy Sahoo
Keyword(s):  
Oxidative Stress ◽  
High Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Transport ◽  
Selective Uptake ◽  
Peripheral Tissues ◽  
Scavenger Receptor Bi ◽  
Hdl Function

High density lipoprotein (HDL) combats atherosclerosis, largely through its role in the reverse cholesterol transport (RCT) pathway where excess cholesterol from peripheral tissues is transported by HDL to the liver for excretion. High HDL-cholesterol (HDL-C) levels have been traditionally linked to a lower risk for cardiovascular disease (CVD). However, recent evidence suggests that HDL “function”, rather than HDL levels, is a better indicator of CVD risk as modifications to HDL under oxidative stress can render the particles “dysfunctional”. Scavenger receptor BI (SR-BI), the HDL receptor, mediates the selective uptake of HDL-cholesteryl ester (CE) into the liver during RCT. We hypothesized that SR-BI would be unable to mediate its cholesterol transport functions in the presence of oxidized or modified HDL due to an inability to engage in productive binding interactions with modified ligands. To test this hypothesis, we assessed HDL binding and selective uptake of HDL-CE in COS7 cells transiently expressing SR-BI using native HDL or HDL modified with: 1) copper (Cu2+), 2) 4-hydroxynonenal (HNE), or 3) acrolein. Our data revealed that, compared to native HDL, SR-BI bound 20-50% less Cu2+-HDL and acrolein-HDL, and mediated 40%-60% less selective uptake of CE from these modified particles, respectively. On the other hand, while SR-BI was able to bind HNE-HDL, it could not efficiently mediate cholesterol uptake (20% less compared to native HDL). Interestingly, our data also revealed that the ability of SR-BI to mediate the release of free cholesterol from COS7 cells did not differ when modified HDL served as acceptor particles, as compared to native HDL. Taken together, only the HDL binding and HDL-CE selective uptake functions of SR-BI are influenced by the type of modification on the HDL particle. These data have significant implications as they suggest that higher levels of plasma HDL-C may, in part, be the result of the inability of SR-BI to recognize and mediate cholesterol removal from HDL particles that have been exposed to oxidative stress. More detailed investigations of the interactions between SR-BI and various populations of oxidized HDL will improve our understanding of the mechanisms that render HDL dysfunctional, and ultimately, atherogenic.

9 High density lipoproteins and reverse cholesterol transport. Lessons from natural mutations

1997 ◽  
Vol 130 ◽  
pp. S4
Author(s):  
A. von Eckardstein ◽  
P. Cullen ◽  
A. Cignarella ◽  
Y. Zhu ◽  
U. Daum ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
High Density ◽  
High Density Lipoproteins ◽  
Cholesterol Transport

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.

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