scholarly journals High-density lipoprotein 3 physicochemical modifications induced by interaction with human polymorphonuclear leucocytes affect their ability to remove cholesterol from cells

1996 ◽  
Vol 314 (1) ◽  
pp. 285-292 ◽  
Author(s):  
Anne COGNY ◽  
Véronique ATGER ◽  
Jean-Louis PAUL ◽  
Théophile SONI ◽  
Nicole MOATTI
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Molar Ratio ◽  
Polymorphonuclear Leucocytes ◽  
Partial Loss ◽  
Apo Ai

1. We have recently reported that a short incubation (60 min) in vitro of high-density lipoprotein (HDL) 3 with human polymorphonuclear leucocytes (PMNs) leads to a proteolytic cleavage of apolipoprotein (apo) AII and to a change in the distribution of apo AI isoforms [Cogny, Paul, Atger, Soni and Moatti (1994) Eur. J. Biochem. 222, 965–973]. Since PMNs have been observed to be present in the earliest atherosclerotic lesions for a number of days, we investigated the HDL3 physicochemical modifications induced by in vitro interaction for a long period of time (24 h) with PMNs and the consequences of the changes on the ability of HDL3 to remove cholesterol from cells. 2. The stimulated PMN modification of HDL3 over 24 h resulted in a partial loss of protein with no variation in lipid molar ratio and a loss of 50% of HDL α-tocopherol content. The decrease in total protein was due first to a complete degradation of apo AII, and secondly to a partial loss of apo AI. The apo AI remaining on the particles was in part hydrolysed and the apo AI-1 isoform was completely shifted to the apo AI-2 isoform. These apo changes were accompanied by a displacement of the native HDL3 apparent size toward predominantly larger particles. 3. The ability of PMN-modified HDL3 to remove 3H-labelled free cholesterol from cells was measured in two cell lines: Fu5AH rat hepatoma cells and J774 mouse macrophages. HDL3 which had only a limited contact with PMNs (60 min) showed only a small non-significant reduction in the efficiency of cholesterol efflux. On the other hand, compared with native HDL3, HDL3 modified by PMNs for 24 h had a markedly reduced ability to remove cholesterol from cells, regardless of the type of cell. 4. The results suggest that PMN-modified HDL3, if occurring in vivo, could contribute to acceleration of the atherogenic process by decreasing the cholesterol efflux from cells.

scholarly journals Nascent HDL (High-Density Lipoprotein) Discs Carry Cholesterol to HDL Spheres

2020 ◽  
Vol 40 (5) ◽  
pp. 1182-1194 ◽  
Author(s):  
Alexei V. Navdaev ◽  
Lorenzo Sborgi ◽  
Samuel D. Wright ◽  
Svetlana A. Didichenko
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Fluorescent Labeling ◽  
High Density ◽  
Atp Binding Cassette Transporter ◽  
Spherical Plasma ◽  
Apo Ai

Objective: To characterize the fate of protein and lipid in nascent HDL (high-density lipoprotein) in plasma and explore the role of interaction between nascent HDL and mature HDL in promoting ABCA1 (ATP-binding cassette transporter 1)-dependent cholesterol efflux. Approach and Results: Two discoidal species, nascent HDL produced by RAW264.7 cells expressing ABCA1 (LpA-I [apo AI containing particles formed by incubating ABCA1-expressing cells with apo AI]), and CSL112, human apo AI (apolipoprotein AI) reconstituted with phospholipids, were used for in vitro incubations with human plasma or purified spherical plasma HDL. Fluorescent labeling and biotinylation of HDL were employed to follow the redistribution of cholesterol and apo AI, cholesterol efflux was measured using cholesterol-loaded cells. We show that both nascent LpA-I and CSL112 can rapidly fuse with spherical HDL. Redistribution of the apo AI molecules and cholesterol after particle fusion leads to the formation of (1) enlarged, remodeled, lipid-rich HDL particles carrying lipid and apo AI from LpA-I and (2) lipid-poor apo AI particles carrying apo AI from both discs and spheres. The interaction of discs and spheres led to a greater than additive elevation of ABCA1-dependent cholesterol efflux. Conclusions: These data demonstrate that although newly formed discs are relatively poor substrates for ABCA1, they can interact with spheres to produce lipid-poor apo AI, a much better substrate for ABCA1. Because the lipid-poor apo AI generated in this interaction can itself become discoid by the action of ABCA1, cycles of cholesterol efflux and disc-sphere fusion may result in net ABCA1-dependent transfer of cholesterol from cells to HDL spheres. This process may be of particular importance in atherosclerotic plaque where cholesterol acceptors may be limiting.

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

Synthesis of recombinant high density lipoprotein with apolipoprotein A-I and apolipoprotein A-V

2011 ◽  
Vol 392 (5) ◽  
Author(s):  
Xinbo Zhang ◽  
Baosheng Chen
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
High Density ◽  
Over Expression ◽  
Apolipoprotein A ◽  
Atherosclerotic Lesion Development

Abstract It has been shown that apolipoprotein A-V (apoA-V) over-expression significantly lowers plasma triglyceride levels and decreases atherosclerotic lesion development. To assess the feasibility of recombinant high density lipoprotein (rHDL) reconstituted with apoA-V and apolipoprotein A-I (apoA-I) as a therapeutic agent for hyperlipidemic disorder and atherosclerosis, a series of rHDL were synthesized in vitro with various mass ratios of recombinant apoA-I and apoA-V. It is interesting to find that apoA-V of rHDL had no effect on lipoprotein lipase (LPL) activation in vitro and very low density lipoprotein (VLDL) clearance in HepG2 cells and in vivo. By contrast, LPL activation and VLDL clearance were inhibited by the addition of apoA-V to rHDL. Furthermore, the apoA-V of rHDL could not redistribute from rHDL to VLDL after incubation at 37°C for 30 min. These findings suggest that an increase of apoA-V in rHDL could not play a role in VLDL clearance in vitro and in vivo, which could, at least in part, attribute to the lost redistribution of apoA-V from rHDL to VLDL and LPL binding ability of apoA-V in rHDL. The therapeutic application of rHDL reconstituted with apoA-V and apoA-I might need the construction of rHDL from which apoA-V could freely redistribute to VLDL.

scholarly journals Clearance from plasma of lymph chylomicrons and chylomicron remnants labelled with 125I-tyramine-cellobiose

1992 ◽  
Vol 286 (3) ◽  
pp. 937-943 ◽  
Author(s):  
H L Ly ◽  
B C Mortimer ◽  
E Baker ◽  
T G Redgrave
Keyword(s):  
High Density Lipoprotein ◽  
Lipoprotein Lipase ◽  
Bovine Milk ◽  
Density Lipoprotein ◽  
High Density ◽  
Low Density ◽  
Apolipoprotein B48 ◽  
Chylomicron Remnants

The aims of the present study were to evaluate the metabolism of chylomicrons (CM) and of CM remnants after labelling with radioactive iodine and converting the iodinated CM into remnants in vitro. Lymph CM were radiolabelled with 125I or sham-labelled with 127I by either the ICl procedure or the tyramine-cellobiose (TC) procedure, then injected into rats. The clearance from plasma of the iodinated CM was compared with control non-iodinated lipid-labelled CM. After iodination with ICl, the plasma removal of endogenously labelled CM was significantly different from non-iodinated CM, with increased uptake of CM triacylglycerols by the liver. In contrast, the clearances from plasma and the uptake by organs of radiolabelled lipids of CM iodinated by the TC method (TC-CM) were similar to control CM. About 40% of the label from 125I-TC-CM was insoluble in 50% propan-2-ol, indicating association with CM apolipoprotein B48. Only about 8% of label was lipid soluble, mostly in phosphatidylethanolamine. Radioactivity from 125I-TC-CM injected intravenously in rats was cleared rapidly and by 30 min only 20% remained in plasma, whereas 48% was recovered in the liver. After fractionation of the plasma by density-gradient ultracentrifugation, most label remained associated with d (relative density) less than 1.006 lipoproteins. In intact rats label was also found associated with the low-density and high-density lipoprotein fractions of plasma. When the liver was excluded from circulation, the recovery of label in low-density- and high-density-lipoprotein fractions was greatly decreased. CM remnants were prepared in vivo by injecting 125I-TC-CM into functionally hepatectomized donors and compared with remnants prepared in vitro by incubation with purified bovine milk lipoprotein lipase. Although remnants prepared in vitro cleared from plasma slower than remnants prepared in vivo, the size, lipid composition and apolipoprotein profile on gradient PAGE of the remnants were similar. We conclude that labelling of CM by the TC method avoided the ‘artefactual’ changes in metabolism seen after labelling by the ICl procedure. CM remnants when prepared in vitro using lipoprotein lipase were found to be similar to those prepared in vivo after injection into functionally hepatectomized rats.

scholarly journals Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery

2020 ◽  
Vol 21 (3) ◽  
pp. 739 ◽  
Author(s):  
Jiansheng Huang ◽  
Dongdong Wang ◽  
Li-Hao Huang ◽  
Hui Huang
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Inverse Correlation ◽  
Hdl Cholesterol ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
New Paradigm

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear.

Abstract 389: Covalent Modifications of Apolipoproteins in High Density Lipoprotein by Oxidized Phospholipids Impair the Cholesterol Efflux Function of High Density Lipoprotein and are Detected in Hyperlipidemic Plasma

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Detao Gao ◽  
Lifang Zhang ◽  
Eugene Podrez
Keyword(s):  
High Density Lipoprotein ◽  
Human Plasma ◽  
Protein Function ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Oxidized Phospholipids ◽  
Protein Adduction ◽  
Covalent Modifications

Oxidized phospholipids (oxPLs) accumulate at sites of oxidative stress and contribute significantly to atherosclerosis and thrombosis. Most oxPLs have electrophilic substituents and are highly likely to form covalent adducts with proteins, thus compromising protein function. Detection of covalent interactions between oxPLs and proteins could provide important information regarding the type of proteins preferentially modified by oxPLs. However, to date, such studies are extremely limited due to significant technical challenges. We now carry out systematic studies on the protein adduction by oxPLs formed in murine and human plasma. Plasma samples were exposed to a physiologically relevant myeloperoxidase/H 2 O 2 /NO 2 – oxidizing system of phagocytes. Protein adduction by the oxPLs generated in plasma was assessed using LC-MS/MS after tryptic digestion and peptide enrichment using a novel method that we developed. We found that HDL apolipoproteins are the major targets of modification by oxPLs in both murine and human plasma. For apoA-I, the most abundant apolipoprotein in HDL, the major modification sites of oxPLs were located in the region (AA144-186), which is critical for the ABCA1 mediated cholesterol efflux to HDL. We further demonstrated that human apoA-I was also heavily crosslinked by specific oxPLs via histidine and lysine residues located in the region (AA144-186) with apoA-I, or other apolipoproteins, including apoA-II, apoA-IV and apoC-I. In vitro experiments demonstrated that oxPLs modification on lipid free apoA-I or nascent HDL (HDL3) dramatically impairs their function as cholesterol efflux mediators. Using hyperlipidemic LDLr-/- mice, we detected a crosslink adduct of apoA-II with apoE by oxPL in murine plasma. To the best of our knowledge, this is the first report for the detection of endogenous protein adducts with oxPLs.

Alteration of high-density lipoprotein functionality in Alzheimer’s disease patients

2017 ◽  
Vol 95 (8) ◽  
pp. 894-903 ◽  
Author(s):  
Paméla Camponova ◽  
Aurélie Le Page ◽  
Hicham Berrougui ◽  
Julie Lamoureux ◽  
Graham Pawelec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Density Lipoprotein ◽  
Healthy Subjects ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Elderly Subjects ◽  
The Difference

The aims of the present study were to determine whether high-density lipoprotein (HDL) functionality-mediated cholesterol efflux is altered in Alzheimer’s disease and to investigate the role and effect of amyloid-beta (Aβ) in the regulation of the anti-atherogenic activity of HDL. Eighty-seven elderly subjects were recruited, of whom 27 were healthy, 27 had mild cognitive impairment (MCI), and 33 had mild Alzheimer’s disease (mAD). Our results showed that total cholesterol levels are negatively correlated with the Mini-Mental State Examination (MMSE) score (r = –0.2602, p = 0.0182). HDL from the mAD patients was less efficient at mediating cholesterol efflux from J774 macrophages (p < 0.05) than HDL from the healthy subjects and MCI patients. While HDL from the MCI patients was also less efficient at mediating cholesterol efflux than HDL from the healthy subjects, the difference was not significant. Interestingly, the difference between the healthy subjects and the MCI and mAD patients with respect to the capacity of HDL to mediate cholesterol efflux disappeared when ATP-binding cassette transporter A1 (ABCA1)-enriched J774 macrophages were used. HDL fluidity was significantly inversely correlated with the MMSE scores (r = –0.4137, p < 0.009). In vitro measurements of cholesterol efflux using J774 macrophages showed that neither Aβ1-40nor Aβ1-42stimulate cholesterol efflux from unenriched J774 macrophages in basal or ABCA1-enriched J774 macrophages.

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