Lipoprotein metabolism and the role of apolipoproteins as metabolic programmers

1985 ◽  
Vol 63 (8) ◽  
pp. 850-869 ◽  
Author(s):  
Peter J. Dolphin
Keyword(s):  
Lipoprotein Metabolism ◽  
Lipid Binding ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Surface Lipid ◽  
Peripheral Tissues ◽  
Lipoprotein Particles ◽  
Catabolic Enzymes ◽  
Surface Lipids

The plasma lipoproteins are large spherical macromolecular structures containing hydrophobic core lipids with phospholipids, cholesterol, and specific proteins (apoproteins) providing an amphipathic interface with the hydrophilic environment of the plasma. The major function of these particles, which are biosynthesized by the intestine and liver, is the transport of dietary or endogenously synthesized lipids to those tissues which utilize exogenous lipids for oxidative metabolism, storage, steroid hormone biosynthesis, or maintenance of their membrane integrity. The triacylglycerol-rich lipoproteins are biosynthesized as metabolically inert particles which are catabolically programmed by postsecretory addition of apoproteins which activate the major lipolytic enzymes, inhibit premature removal, and ensure the later interaction of the degraded particles with specific cellular receptors. During the course of lipolysis, those apoproteins which activate catabolic enzymes are lost from the lipoprotein particles and are transferred to the high-density lipoproteins from which they were initially acquired. High-density lipoprotein also mediates the removal of cholesterol deposited in peripheral tissues as a result of uptake of degraded triacylglycerol-rich lipoproteins. Acquisition of cellular cholesterol by high-density lipoproteins results in its apoprotein-stimulated esterification and the later addition of an apoprotein which mediates receptor recognition and removal of the particle from the plasma. The presence or absence of specific apoproteins on the surface of a lipoprotein particle is modulated by the lipid-binding properties of the apoprotein, the surface lipid composition, and the size of the particle. The nature and mass ratios of these surface lipids are themselves dependent upon the activity of apoprotein-stimulated catabolic enzymes and other proteins which mediate the exchange of surface lipids between lipoprotein particles. Thus the apoproteins are effective programmers of lipoprotein metabolism and fulfil their role as such by cycling, in a directed fashion, between nascent and existing plasma lipoproteins. Genetic defects resulting in a perturbation of this intricate mechanism can lead to premature and pronounced atherosclerosis.

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.

scholarly journals IMMUNOCHEMICAL STUDIES ON HUMAN PLASMA LIPOPROTEINS

1957 ◽  
Vol 105 (1) ◽  
pp. 49-67 ◽  
Author(s):  
Frederick Aladjem ◽  
Miriam Lieberman ◽  
John W. Gofman
Keyword(s):  
Human Plasma ◽  
Plasma Protein ◽  
Protein Fraction ◽  
Low Density Lipoproteins ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Plasma Protein Fraction ◽  
Free Plasma

Low density human plasma lipoproteins Sf 17+, Sf 13, and Sf 6, high density lipoproteins 2 and 3, and a lipoprotein-free plasma protein fraction were isolated from human plasma by ultracentrifugal methods. It was found that human plasma lipoproteins are immunochemically distinct from the non-lipoprotein containing plasma protein fraction. Lipoprotein fractions of a given hydrated density, isolated from different individuals, were found to be immunochemically indistinguishable by qualitative absorption tests. Qualitative antigenic differences were shown to exist between low density lipoproteins and high density lipoproteins. Quantitative precipitin reactions showed that low density lipoproteins Sf 6 and Sf 13 were immunochemically very similar. However, they differed with respect to the amount of antigen nitrogen required for maximum precipitation. Agar diffusion analyses were performed; the results suggest heterogeneity of lipoproteins by this criterion.

scholarly journals Agent-Based Modeling Predicts HDL-independent Pathway of Removal of Excess Surface Lipids from Very Low Density Lipoprotein

2018 ◽  
Author(s):  
Yared Paalvast ◽  
Jan Albert Kuivenhoven ◽  
Barbara M. Bakker ◽  
Albert .K. Groen
Keyword(s):  
Lipoprotein Metabolism ◽  
Hdl Cholesterol ◽  
High Plasma ◽  
Surface Lipid ◽  
Agent Based ◽  
Plasma Triglycerides ◽  
Excess Surface ◽  
Surface Lipids ◽  
Low Hdl ◽  
Experimental Findings

AbstractA hallmark of the metabolic syndrome is low HDL-cholesterol coupled with high plasma triglycerides (TG), but it is unclear what drives this close association. Plasma triglycerides and HDL cholesterol are thought to communicate through two distinct mechanisms. Firstly, excess surface lipids from VLDL released during lipolysis are transferred to HDL, thereby contributing to HDL directly but also indirectly through providing substrate for LCAT. Secondly, high plasma TG increases clearance of HDL through core-lipid exchange between VLDL and HDL via CETP and subsequent hydrolysis of the TG in HDL, resulting in smaller HDL and thus increased clearance rates.To test our understanding of how high plasma TG induces low HDL-cholesterol, making use of established knowledge, we developed a comprehensive agent-based model of lipoprotein metabolism which was validated using monogenic disorders of lipoprotein metabolism.By perturbing plasma TG in the model, we tested whether the current theoretical framework reproduces experimental findings. Interestingly, while increasing plasma TG through simulating decreased lipolysis of VLDL resulted in the expected decrease in HDL cholesterol, perturbing plasma TG through simulating increased VLDL production rates did not result in the expected HDL-TG relation at physiological lipid fluxes. However, model perturbations and experimental findings can be reconciled if we assume a pathway removing excess surface-lipid from VLDL that does not contribute to HDL cholesterol ester production through LCAT. In conclusion, our model simulations suggest that excess surface lipid from VLDL is cleared in part independently from HDL.Author summaryWhile it has long been known that high plasma triglycerides are associated with low HDL cholesterol, the reason for this association has remained unclear. One of the proposed mechanisms is that during catabolism of VLDL, lipoproteins rich in triglyceride, the excess surface of these particles become a source for the production of HDL cholesterol, and that therefore decreased catabolism of VLDL will lead to both higher plasma triglyceride and low HDL cholesterol. Another proposed mechanism is that during increased production of VLDL, there will be increased exchange of core lipids between VLDL and HDL, with subsequent hydrolysis of the triglyceride in HDL, leading to smaller HDL that is cleared more rapidly. To investigate these mechanisms further we developed a computational model based on established knowledge concerning lipoprotein metabolism and validated the model with known findings in monogenetic disorders. Upon perturbing the plasma triglycerides within the model by increasing the VLDL production rate, we unexpectedly found an increase in both triglyceride and HDL cholesterol. However, upon assuming that less excess surface lipid is available to HDL, HDL decreases in response to increased VLDL production. We therefore propose that there must be a pathway removing excess surface lipids that is independent from HDL.AbbreviationsPR(production rate)FCR(fractional catabolic rate)ppd(pool per day)SRB1(scavenger receptor B1)EL(endothelial lipase)HL(hepatic lipase)PLTP(phospholipid transfer protein)CETP(cholesteryl ester transfer protein)FC(free cholesterol)CE(cholesterol ester)PL(phospholipid)LpX(lipoprotein X).

Thromboplastic Effects ot Human Plasma Lipoproteins

1975 ◽  
Author(s):  
L.-O. Andersson ◽  
H. Sandberg
Keyword(s):  
Human Plasma ◽  
Platelet Rich Plasma ◽  
Density Lipoprotein ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Phospholipid Content ◽  
Factor X ◽  
Promoting Effect ◽  
Free Plasma

Lipoprotein fractions from human plasma was prepared by ultracentrifugal flotation. Additions of those fractions to plasma containing various amounts of platelets showed that in platelet-poor and platelet-free plasma there was a clear clot-promoting effect of the additions. In platelet-rich plasma, this effect was negligible. Measurements on the thrombo-plastine and Stypven clotting times showed that the high density lipoprotein fraction affected both the prothrombin and the Factor X activation steps whereas the low density lipoproteins only influenced the prothrombin activation step. Addition of antibodies against high density lipoproteins to platelet-free plasma caused a prolongation of the thromboplastin time.The relation between lipoprotein structure, phospholipid content and thromboplastic effects is dicussed.

Effects of triton WR 1339 and heparin on the transfer of surface lipids from triglyceride-rich emulsions to high density lipoproteins in rats

Lipids ◽  
1990 ◽  
Vol 25 (11) ◽  
pp. 701-705 ◽  
Author(s):  
Raul C. Maranhão ◽  
Ivete A. Roland ◽  
Mário H. Hirata
Keyword(s):  
High Density ◽  
High Density Lipoproteins ◽  
Triton Wr 1339 ◽  
Surface Lipids

scholarly journals Characterization of plasma lipoproteins separated and purified by agarose-column chromatography

1974 ◽  
Vol 139 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Lawrence L. Rudel ◽  
Jason A. Lee ◽  
Manford D. Morris ◽  
James M. Felts
Keyword(s):  
Human Plasma ◽  
Column Chromatography ◽  
Low Density Lipoproteins ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Simple Method ◽  
Lipoprotein Class

1. A simple method for isolation of individual human plasma lipoprotein classes is presented. In this technique, lipoproteins are removed from plasma at d1.225 by ultracentrifugation, after which they are separated and purified by agarose-column chromatography. 2. Three major classes are obtained after agarose-column chromatography. Separation between classes is excellent; more than 95% of the lipoproteins eluted from the column are recovered in the form of a purified lipoprotein class. 3. Each lipoprotein class was characterized immunologically, chemically, electrophoretically and by electron microscopy. A comparison of the properties of the column-isolated lipoproteins was made with very-low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins separated by sequential ultracentrifugation at densities of 1.006, 1.063 and 1.21 respectively. 4. By each criterion, peak-I lipoproteins from the agarose column are the same as very-low-density lipoproteins, peak-II lipoproteins are the same as low-density lipoproteins, and peak-III lipoproteins are the same as high-density lipoproteins. Thus the lipoprotein classes isolated by both methods are similar if not identical. 5. The agarose-column separation technique offers the advantage of a two- to three-fold saving in time. In addition, the column-elution pattern serves as a recording of the size distribution of lipoproteins in plasma. 6. The most complete characterization is reported for human plasma lipoproteins. The results with rhesus-monkey and rabbit lipoproteins were identical.

scholarly journals The Role of High Density Lipoproteins in Thrombosis

2002 ◽  
Vol 2 ◽  
pp. 89-95 ◽  
Author(s):  
Marina Cuchel ◽  
Daniel J. Rader
Keyword(s):  
Potential Role ◽  
Strong Association ◽  
Coagulation Factors ◽  
Scientific Data ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Anionic Phospholipids ◽  
Lipids And Lipoproteins

Lipids and lipoproteins, as well as factors involved in hemostasis and thrombosis, play a central role in the pathogenesis of cardio- and cerebrovascular disease. In recent years it has become clear that a strong association exists between coagulation factors and plasma lipoproteins. Anionic phospholipids are necessary for the optimal activity of both pro- and anticoagulant enzymatic complexes. Cell membranes have traditionally been considered to provide the essential lipid-containing surfaces. However, in light of recent studies, plasma lipoproteins are also believed to provide appropriate surfaces to support coagulation. While triglyceride-rich lipoproteins and oxidized low-density lipoproteins are associated with a procoagulant profile, high-density lipoproteins (HDL) may have an anticoagulant effect. This paper reviews scientific data on the potential role of HDL as modulator of thrombotic processes.

scholarly journals Ghrelin Interacts with Human Plasma Lipoproteins

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2355-2362 ◽  
Author(s):  
Carine De Vriese ◽  
Mirjam Hacquebard ◽  
Françoise Gregoire ◽  
Yvon Carpentier ◽  
Christine Delporte
Keyword(s):  
Platelet Activating Factor ◽  
Peptide Hormone ◽  
Hydrolytic Activity ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Rat Serum ◽  
Gh Secretion ◽  
Acyl Ghrelin

Ghrelin, a peptide hormone produced predominantly by the stomach, stimulates food intake and GH secretion. The Ser3 residue of ghrelin is mainly modified by a n-octanoic acid. In the human bloodstream, ghrelin circulates in two forms: octanoylated and desacylated. We previously demonstrated that ghrelin is desoctanoylated in human serum by butyrylcholinesterase (EC 3.1.1.8) and other esterase(s), whereas in rat serum, only carboxylesterase (EC 3.1.1.1) is involved. The aims of this study were to determine the role of lipoprotein-associated enzymes in ghrelin desoctanoylation and the role of lipoproteins in the transport of circulating ghrelin. Our results show that ghrelin desoctanoylation mostly occurred in contact with low-density lipoproteins (LDLs) and lipoprotein-poor plasma subfractions. Butyrylcholinesterase and platelet-activating factor acetylhydrolase (EC 3.1.1.47) were responsible for the ghrelin hydrolytic activity of the lipoprotein-poor plasma and LDL subfractions, respectively. Moreover, we observed that ghrelin is associated with triglyceride-rich lipoproteins (TRLs), high-density lipoproteins (HDLs), very high-density lipoproteins (VHDLs), and to some extent LDLs. In conclusion, we report that the presence of the acyl group is necessary for ghrelin interaction with TRLs and LDLs but not HDLs and VHDLs. Ghrelin interacts via its N- and C-terminal parts with HDLs and VHDLs. This suggests that, whereas TRLs mostly transport acylated ghrelin, HDLs and VHDLs transport both ghrelin and des-acyl ghrelin.

scholarly journals Species Differences in the Proportion of Plasma Lipoprotein Lipid Carried by High-Density Lipoproteins Influence the Distribution of Free and Liposomal Nystatin in Human, Dog, and Rat Plasma

1999 ◽  
Vol 43 (6) ◽  
pp. 1424-1428 ◽  
Author(s):  
Manisha Ramaswamy ◽  
Thomas L. Wallace ◽  
Paul A. Cossum ◽  
Kishor M. Wasan
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Rat Plasma ◽  
High Density ◽  
Plasma Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Lipoprotein Lipid ◽  
Triglyceride Rich Lipoprotein

ABSTRACT The objective of this study was an interspecies comparison of free nystatin (NYS) and liposomal NYS (Nyotran) distribution in plasma. NYS and liposomal NYS at concentrations of 5, 10, and 20 μg of NYS/ml were incubated in human, dog, and rat plasma for 5, 60, and 180 min at 37°C. Following these incubations, plasma samples were separated into their high-density lipoprotein (HDL), triglyceride-rich lipoprotein, low-density lipoprotein, and lipoprotein-deficient plasma (LPDP) fractions by density-gradient ultracentrifugation, and each fraction was assayed for NYS by high-pressure liquid chromatography. Total plasma and lipoprotein cholesterol, triglyceride, and protein concentrations in each human, dog, or rat plasma sample were determined by enzymatic assays. When NYS and liposomal NYS were incubated in human, dog, or rat plasma, the majority of the NYS was recovered in the LPDP fraction. For the 5- and 60-min incubation times for all plasmas measured, a significantly greater percentage of NYS was recovered in the lipoprotein fraction (primarily HDL) following the incubation of liposomal NYS than following the incubation of NYS. There was a significant correlation between the lipoprotein lipid and protein profiles in human, dog, and rat plasmas and the distribution of NYS and liposomal NYS in plasma. In particular, differences in the proportion of plasma lipoprotein cholesterol, triglyceride, and apolar lipids (cholesteryl ester and triglycerides) carried by HDL influenced the distribution of NYS and liposomal NYS within plasmas of different species. These findings suggest that the distribution of NYS among plasma lipoproteins of different species is defined by the proportion of lipid carried by HDL, and this is possibly an important consideration when evaluating the pharmacokinetics, toxicities, and activities of these compounds following administration to different animal species.

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