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At least 19 recordsLinked to original sources
PubMed1992

Mechanisms by which lipoprotein lipase alters cellular metabolism of lipoprotein(a), low density lipoprotein, and nascent lipoproteins. Roles for low density lipoprotein receptors and heparan sulfate proteoglycans.

We sought to investigate effects of lipoprotein lipase (LpL) on cellular catabolism of lipoproteins rich in apolipoprotein B-100. LpL increased cellular degradation of lipoprotein(a) (Lp(a)) and low density lipoprotein (LDL) by 277% +/- 3.8% and 32.5% +/- 4.1%, respectively, and cell association by 509% +/- 8.7% and 83.9% +/- 4.0%. The enhanced degradation was entirely lysosomal. Enhanced degradation of Lp(a) had at least two components, one LDL receptor-dependent and unaffected by heparitinase digestion of the cells, and the other LDL receptor-independent and heparitinase-sensitive. The effect of LpL on LDL degradation was entirely LDL receptor-independent, heparitinase-sensitive, and essentially absent from mutant Chinese hamster ovary cells that lack cell surface heparan sulfate proteoglycans. Enhanced cell association of Lp(a) and LDL was largely LDL receptor-independent and heparitinase-sensitive. The ability of LpL to reduce net secretion of apolipoprotein B-100 by HepG2 cells by enhancing cellular reuptake of nascent lipoproteins was also LDL receptor-independent and heparitinase-sensitive. None of these effects on Lp(a), LDL, or nascent lipoproteins required LpL enzymatic activity. We conclude that LpL promotes binding of apolipoprotein B-100-rich lipoproteins to cell surface heparan sulfate proteoglycans. LpL also enhanced the otherwise weak binding of Lp(a) to LDL receptors. The heparan sulfate proteoglycan pathway represents a novel catabolic mechanism that may allow substantial cellular and interstitial accumulation of cholesteryl ester-rich lipoproteins, independent of feedback inhibition by cellular sterol content.

Animals↗
PubMed2000

Distribution of lipid-soluble antioxidants in lipoproteins from healthy subjects. I. Correlation with plasma antioxidant levels and composition of lipoproteins.

The concentration of five lipid-soluble antioxidants (gamma- and alpha-tocopherol, lycopene, beta-carotene and ubiquinol-10) was measured in plasma and very low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) isolated from young healthy normo- cholesterolemic subjects. Alpha-tocopherol was the exclusive antioxidant whose plasma concentration significantly correlated with the absolute concentration of total cholesterol (r =0.541, P<0.001). No correlation was found between plasma concentration and lipoprotein content of alpha-tocopherol and ubiquinol-10, whereas it reached statistically significant values for gamma-tocopherol, lycopene and beta-carotene. The alpha-tocopherol content in VLDL and HDL, but not in LDL, was strictly associated with the relative abundance of cholesterol and phospholipids in the lipoprotein particles. Moreover, the difference between alpha-tocopherol concentration in VLDL and LDL appeared to be strictly related to the differences in cholesterol, phospholipids and triglycerides. The percent distribution of the total plasma pool of antioxidant in each lipoprotein class revealed that gamma- and alpha-tocopherol were roughly equally distributed in LDL and HDL. On the other hand, lycopene, beta-carotene and ubiquinol-10 were preferentially sequestered in LDL. Finally, the absolute and relative concentration of alpha-tocopherol, but not that of other antioxidants, in HDL exhibited a statistically significant correlation with plasma HDL/LDL cholesterol ratio. These findings indicate that: (i) plasma concentrations of major lipid-soluble antioxidants are not always predictive of their levels in lipoproteins and that, within individual lipoprotein classes, (ii) the lipid composition, metabolism and relative plasma concentration may significantly affect their abundance.

Adult↗
PubMed1991

Plasma distribution of cyclosporine within lipoproteins and "in vitro" transfer between very-low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins.

Cyclosporine A (CsA) is a very lipophilic, immunosuppressive peptide that is highly bound (greater than 95%) in plasma. Approximately 50% of the drug is bound to lipoproteins and the remainder to erythrocytes. Neither the therapeutic nor the toxic effects of cyclosporine have been correlated with the free drug concentration. It has been proposed that low-density lipoprotein (LDL) delivers CsA to T-lymphocytes via the LDL receptor pathway, where it then produces its therapeutic effects. We have found that our patients chronically treated with cyclosporine carry as much or more CsA in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and high-density lipoprotein (HDL) as they do in LDL. In addition, as previously reported, those patients with high VLDL carried the major portion of CsA in their VLDL subfraction. Moreover, the triglyceride-rich lipoproteins (VLDL and IDL) were found to contain much more CsA per mg of lipid than either HDL or LDL. An acute drug challenge led to the same CsA distribution as that seen in the chronically treated patients. "In vitro" incubations of lipoproteins containing CsA with lipoproteins from untreated individuals demonstrated a different relative affinity of CsA for the various lipoproteins than would be predicted from the plasma distribution: LDL greater than VLDL greater than HDL. We propose that the plasma distribution of CsA is determined by factors other than simple diffusion between the lipoprotein particles. Possible mechanisms would include (a) plasma factors that augment or inhibit CsA transfer or (b) metabolic processing of the lipoproteins that move CsA from one lipoprotein to another.

Adolescent↗
PubMed1986

Lipolytic degradation of human very low density lipoproteins by human milk lipoprotein lipase: the identification of lipoprotein B as the main lipoprotein degradation product.

Although the direct conversion of very low density lipoproteins (VLDL) into low density (LDL) and high density (HDL) lipoproteins only requires lipoprotein lipase (LPL) as a catalyst and albumin as the fatty acid acceptor, the in vitro-formed LDL and HDL differ chemically from their native counterparts. To investigate the reason(s) for these differences, VLDL were treated with human milk LPL in the presence of albumin, and the LPL-generated LDL1-, LDL2-, and HDL-like particles were characterized by lipid and apolipoprotein composition. Results showed that the removal of apolipoproteins B, C, and E from VLDL was proportional to the degree of triglyceride hydrolysis with LDL2 particles as the major and LDL1 and HDL + VHDL particles as the minor products of a complete in vitro lipolysis of VLDL. In comparison with native counterparts, the in vitro-formed LDL2 and HDL + VHDL were characterized by lower levels of triglyceride and cholesterol ester and higher levels of free cholesterol and lipid phosphorus. The characterization of lipoprotein particles present in the in vitro-produced LDL2 showed that, as in plasma LDL2, lipoprotein B (LP-B) was the major apolipoprotein B-containing lipoprotein accounting for over 90% of the total apolipoprotein B. Other, minor species of apolipoprotein B-containing lipoproteins included LP-B:C-I:E and LP-B:C-I:C-II:C-III. The lipid composition of in vitro-formed LP-B closely resembled that of plasma LP-B. The major parts of apolipoproteins C and E present in VLDL were released to HDL + VHDL as simple, cholesterol/phospholipid-rich lipoproteins including LP-C-I, LP-C-II, LP-C-III, and LP-E. However, some of these same simple lipoprotein particles were present after ultracentrifugation in the LDL2 density segment because of their hydrated density and/or because they formed, in the absence of naturally occurring acceptors (LP-A-I:A-II), weak associations with LP-B. Thus, the presence of varying amounts of these cholesterol/phospholipid-rich lipoproteins in the in vitro-formed LDL2 appears to be the main reason for their compositional difference from native LDL2. These results demonstrate that the formation of LP-B as the major apolipoprotein B-containing product of VLDL lipolysis only requires LPL as a catalyst and albumin as the fatty acid acceptor. However, under physiological circumstances, other modulating agents are necessary to prevent the accumulation and interaction of phospholipid/cholesterol-rich apolipoprotein C- and E-containing particles.

Apolipoproteins B↗
PubMed1987

Gradient acrylamide/agarose gels for electrophoretic separation of intact human very low density lipoproteins, intermediate density lipoproteins, lipoprotein a, and low density lipoproteins.

An exponential gradient gel with 0-10% acrylamide and 0.5% agarose was developed for electrophoresis of intact high molecular weight lipoproteins. This system resolves very low density lipoproteins, intermediate density lipoproteins, lipoprotein a, and low density lipoproteins in a size-dependent fashion. The characteristic relative mobility of these species can be determined in relation to protein and colloidal gold reference materials. Electron microscopy of selected lipoprotein fractions confirmed that relative mobility was related to apparent lipoprotein diameter. The composite gel medium can be used with prestained lipoproteins and permits immunoelectroblotting for qualitative analysis of apolipoprotein constituents.

Electrochemistry↗
PubMedDate not supplied

Lipid transport in the avian species. Part 2. Isolation and characterization of lipoprotein A and lipoprotein B, two major lipoprotein families of the male turkey serum lipoprotein system.

(1) Male turkey serum contains two major lipoprotein families designated as LP-A and LP-B in its lipoprotein density classes. These two lipoprotein families were separated from each of the lipoprotein density classes by affinity chromatography on concanavalin A-Sepharose 4B. LP-A was present in the unretained and LP-B in the retained fractions. Both lipoprotein families were characterized by determination of their immunological and electrophoretic properties, the flotation coefficient and chemical composition. (2) LPb was distributed over a wider density range than LP-A. Seventy-four percent of LP-B was found in the LDL, 17% IN The VLDL and 8% in the HDL. In contrast, 98% of LP-A was present in the HDL and 2% in the LDL fractions: there were only trace amounts of LP-A in the VLDL. (3)Immunological and electrophoretic studies showed that the protein moiety of LP-A contained only the two non-identical A-I and A-II polypeptides of ApoA. The protein moiety of LP-B consisted only of ApoB. (4) Isolation of LP-A and LP-B from the major lipoprotein density classes provided further experimental evidence to confirm the existence of chemically distinct lipoprotein families as the fundamental physical-chemical entities of the serum lipoprotein system.

Animals↗
PubMed1993

Lipoprotein lipase and sphingomyelinase synergistically enhance the association of atherogenic lipoproteins with smooth muscle cells and extracellular matrix. A possible mechanism for low density lipoprotein and lipoprotein(a) retention and macrophage foam cell formation.

Prominent features of atheromata include smooth muscle cells, cholesteryl ester-loaded macrophage foam cells, extracellular matrix, extracellularly trapped and aggregated lipoproteins, and various enzymes including lipoprotein lipase (LpL) and sphingomyelinase (SMase). The interplay of these factors was investigated in cell culture. Incubation of bovine aortic smooth muscle cells for 18 h at 37 degrees C with low density lipoprotein (LDL) in the presence of LpL and SMase led to massive aggregation of LDL on the surface of the cells as viewed by phase, fluorescence (using 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate-LDL), and electron microscopy. This aggregation required both enzymes. Studies with 125I-LDL confirmed these observations: 125I-LDL cell association in the presence of LpL plus SMase was 50-100-fold greater than in the absence of the two enzymes and was 10-fold greater than in the presence of either enzyme alone. A similar effect (68-fold enhancement) was seen with 125I-labeled lipoprotein(a) (Lp(a)), another atherogenic lipoprotein. In all cases, 125I-lipoprotein degradation was relatively low (< 5% of cell-associated material). LpL/SMase-mediated association of 125I-LDL with smooth muscle cells was still observed when enzymatically inactive LpL was used. The effect was markedly diminished when the smooth muscle cells were treated with a combination of chondroitin ABC lyase and heparitinase or when mutant Chinese hamster ovary cells that lack cell-surface proteoglycans were used, indicating a specific role for cellular proteoglycans. When smooth muscle cells with 125I-LDL or 125I-Lp(a) aggregates were rinsed and then coincubated with mouse peritoneal macrophages for a further 24 h, visible aggregates disappeared, and there was marked 125I-lipoprotein degradation. Electron micrographs after 24 h of co-culture showed lipid-laden, foamy macrophages situated on top of smooth muscle cells, suggesting that the macrophages phagocytosed and metabolized the smooth muscle cell-associated LDL aggregates. Last, 125I-LDL association with smooth muscle cell extracellular matrix was also synergistically enhanced by LpL and SMase, to a level that was 19-fold greater than in the absence of the two enzymes. Thus, the interaction of LDL and Lp(a) with four atheroma components, namely, smooth muscle cells, extracellular matrix, LpL, and SMase, represents a physiologically plausible mechanism for massive, focal retention and aggregation of atherogenic lipoproteins in the arterial wall with subsequent macrophage foam cell formation.

Animals↗
PubMed1990

Detection of new epitopes formed upon oxidation of low-density lipoprotein, lipoprotein (a) and very-low-density lipoprotein. Use of an antiserum against 4-hydroxynonenal-modified low-density lipoprotein.

4-Hydroxynonenal (HNE) is a major aldehydic propagation product formed during peroxidation of unsaturated fatty acids. The aldehyde was used to modify freshly prepared human low-density lipoprotein (LDL). A polyclonal antiserum was raised in the rabbit and absorbed with freshly prepared LDL. The antiserum did not react with human LDL, but reacted with CuCl2-oxidized LDL and in a dose-dependent manner with LDL, modified with 1, 2 and 3 mM-HNE, in the double-diffusion analysis. LDL treated with 4 mM of hexanal or hepta-2,4-dienal or 4-hydroxyhexenal or malonaldehyde (4 or 20 mM) did not react with the antiserum. However, LDL modified with 4 mM-4-hydroxyoctenal showed a very weak reaction. Lipoprotein (a) and very-low-density lipoprotein were revealed for the first time to undergo oxidative modification initiated by CuCl2. This was evidenced by the generation of lipid hydroperoxides and thiobarbituric acid-reactive substances, as well as by a marked increase in the electrophoretic mobility. After oxidation these two lipoproteins also reacted positively with the antiserum against HNE-modified LDL.

Adult↗
PubMed1992

Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism.

BACKGROUND AND PURPOSE: The role of lipoprotein abnormalities in the development of ischemic cerebrovascular disease has not been sufficiently clarified. The aim of this study was to identify the lipoprotein profile in ischemic cerebrovascular disease and the possible role of apolipoprotein E polymorphism. METHODS: The relation between the concentrations of lipoprotein(a), intermediate density lipoproteins, apolipoprotein A-I, apolipoprotein B, apolipoprotein E, and other lipoproteins was studied in 100 men with ischemic cerebrovascular disease (48 atherothrombotic, 28 lacunar, and 24 of unknown type) and in 100 healthy age-matched men as a control group. RESULTS: Patients with ischemic cerebrovascular disease had significantly higher levels of lipoprotein(a), lipids carried by intermediate density lipoproteins, and low density lipoprotein cholesterol and lower levels of high density lipoproteins than control subjects. Patients with atherothrombotic infarction had higher total serum cholesterol and low density lipoprotein cholesterol concentrations than patients with lacunar infarction. To assess lipoprotein abnormalities in normolipidemic subjects, a subgroup of 38 patients with ischemic cerebrovascular disease and 53 control subjects, both with serum cholesterol levels < 5.2 mmol/l (200 mg/dl) and triglycerides < 2.3 mmol/l (200 mg/dl), was analyzed. Serum lipoprotein(a), lipids carried by very low density lipoproteins and intermediate density lipoproteins, and low density lipoprotein triglycerides were significantly higher in normolipidemic patients compared with normolipidemic control subjects, whereas high density lipoprotein cholesterol levels were lower. Apolipoprotein E polymorphism in our ischemic cerebrovascular patients differed from that of the control group, with the epsilon 4 allele being more prevalent. CONCLUSIONS: Increased serum lipoprotein(a) levels and intermediate density lipoprotein abnormalities together with decreased high density lipoprotein levels are major risk factors for ischemic cerebrovascular disease, even in normocholesterolemic and normotriglyceridemic subjects. Finally, the epsilon 4 allele could probably be a predisposing genetic marker for ischemic cerebrovascular disease.

Adult↗
PubMed1997

Plasma lipoproteins from patients with poorly controlled diabetes mellitus and "in vitro" glycation of lipoproteins enhance the transfer rate of cholesteryl ester from HDL to apo-B-containing lipoproteins.

Alterations in the reverse cholesterol transport system have been described in diabetic mellitus patients in several but not all studies. Furthermore, recently published investigations suggest that a faster "in vitro" transfer rate of cholesteryl ester from high density lipoproteins to apoB-containing lipoproteins could be solely ascribed to variation of the plasma lipoprotein composition and concentration in the diabetic state. The present study analysed the influence of lipoprotein glycation on the cholesteryl ester transfer protein-mediated transfer of esterified cholesterol from high density lipoprotein and its subfractions to lighter density lipoproteins. For this purpose two sets of "in vitro" experiments were carried out utilizing:1) plasma lipoproteins drawn from diabetic and from normal subjects and; 2) normal lipoproteins or partially purified cholesteryl ester transfer protein submitted to "in vitro" glycation. The transfer rate of 14C-cholesteryl ester labelled HDL subfractions to low or very low density lipoproteins was measured in all experiments. After incubations with plasma d > 1.21 g/ml or with purified cholesteryl ester transfer protein, apoB-containing lipoproteins were precipitated with a dextran sulfate/MgCl2 solution. The "in vitro" glycation of the partially purified cholesteryl ester transfer protein, markedly impaired its activity. However, greater transfer rates were observed when lipoproteins from diabetic individuals or the "in vitro" glycated lipoproteins were utilized. This effect was attributed to glycation of the protein component of HDL. In conclusion, lipoprotein glycation elicits an enrichment of the apoB-containing lipoproteins with cholesteryl ester that is likely related to the premature atherosclerosis in patients with poorly controlled diabetes.

Apolipoproteins B↗
PubMed1994

A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cells.

It has previously been shown that lipoprotein lipase can mediate uptake of remnant lipoprotein particles via binding to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP). Binding of lipoprotein lipase, and of triglyceride-rich lipoproteins associated with the lipase, to LRP depends on an intact carboxyl-terminal folding domain of the lipase (Nykjaer, A., Bengtsson-Olivecrona, G., Lookene, A., Moestrup, S. K., Petersen, C. M., Weber, W., Beisiegel, W., and Gliemann, J. (1993) J. Biol. Chem. 268, 15048-15055). Here we show that the site for binding to the receptor is within residues 380-425 of the bovine and residues 378-423 of the human lipoprotein lipase. We demonstrate that a carboxyl-terminal fragment of human lipoprotein lipase (residues 378-448), expressed as fusion protein in Escherichia coli, binds to purified and cellular LRP but not to lipoproteins. Binding of the fragment to purified LRP was blocked by heparin. In addition, the fragment inhibited the binding of lipase and the lipase-mediated binding of lipoproteins to the purified receptor. The fragment exhibited reduced binding to proteoglycan-deficient cells. Moreover, the fragment inhibited the uptake of lipoproteins in cells mediated by the lipase via binding to heparan sulfate proteoglycans and LRP. We conclude that the fragment contains the site for binding to LRP and a candidate site for interaction with heparan sulfate proteoglycans, whereas binding to lipoproteins is inefficient. The fragment can therefore inhibit the lipase-mediated lipoprotein uptake, a process that may promote the development of atherosclerosis when occurring in cells of the arterial wall.

Amino Acid Sequence↗
PubMed1993

Lipoprotein lipase induces catabolism of normal triglyceride-rich lipoproteins via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in vitro. A process facilitated by cell-surface proteoglycans.

Bovine milk lipoprotein lipase (LPL) induced binding, uptake, and degradation of 125I-labeled normal human triglyceride-rich lipoproteins by cultured mutant fibroblasts lacking LDL receptors. The induction was dose-dependent and occurred whether LPL and 125I-lipoproteins were added to incubation media simultaneously or LPL was allowed to bind to cell surfaces, and unbound LPL was removed by washing prior to the assay. Lipolytic modification of lipoproteins did not appear to be necessary for increased catabolism because the effect of LPL was not prevented by inhibitors of LPL's enzymatic activity, p-nitrophenyl N-dodecylcarbamate or phenylmethylsulfonyl fluoride. However, the effect was abolished by boiling LPL prior to the assay suggesting that major structural features of LPL were required. Also, LPL-induced binding to cells was blocked by an anti-LPL monoclonal antibody but not by antibodies that are known to block apolipoprotein E- or B-100-mediated binding to low density lipoprotein (LDL) receptors. This indicates that LPL itself mediated 125I-lipoprotein binding to cells. Cellular degradation of 125I-lipoproteins was partially or completely blocked by two previously described ligands for the LDL receptor-related protein/alpha 2-macroglobulin receptor (LRP): activated alpha 2-macroglobulin (alpha 2M*), and the 39-kDa receptor-associated protein. These data implicated LRP as mediating LPL-induced lipoprotein degradation and were confirmed by showing that LPL's effects were prevented by an immunoaffinity-isolated polyclonal antibody against LRP. Furthermore, LPL promoted binding of 125I-lipoproteins to highly purified LRP in a solid-phase assay. Heparin or heparinase treatment of cells markedly decreased LPL-induced binding, uptake, and degradation of lipoproteins, but had no effect on catabolism of alpha 2M*. Thus, cell-surface proteoglycans were obligatory participants in the effects of LPL but were not required for LRP-mediated catabolism of alpha 2M*. Taken together, these in vitro findings establish that through interaction with cell-surface proteoglycans, LPL induces catabolism of normal human triglyceride-rich lipoproteins via LRP.

Animals↗
PubMed1989

Assessment of lipoprotein activators of skim milk lipoprotein lipase and the relationship between lipoprotein lipase activity and milk fat synthesis.

Bovine plasma and lipoproteins isolated by gel filtration chromatography were examined for their ability to activate skim milk lipoprotein lipase. Addition of equal amounts of protein from either triglyceride-rich lipoprotein, low density lipoprotein, high density lipoprotein or plasma to a lipoprotein lipase assay resulted in 6.0, 2.2, 2.5, or 1.1% hydrolysis of radiolabelled triglyceride emulsion. Lipoprotein lipase activity in skim milk was evaluated as an indicator of mammary lipid secretory capacity. Skim milk lipoprotein lipase activity was significantly lower immediately prepartum as compared with activity immediately postpartum (.2 vs. 5.4% of substrate hydrolyzed). Skim milk lipoprotein lipase was significantly higher during the final 12 d of lactation than in samples obtained 12 d after machine milking was terminated (5.6 vs. less than 1% of substrate hydrolyzed). Although skim milk lipoprotein lipase activity appeared positively related to mammary lipid secretory capacity during the time immediately surrounding initiation and cessation of copious milk production, activity between those periods was not correlated to milk fat percentage, milk fat yield, or stage of lactation.

Animals↗
PubMed1995

Enhancement of the binding of triglyceride-rich lipoproteins to the very low density lipoprotein receptor by apolipoprotein E and lipoprotein lipase.

The low-density lipoprotein (LDL) receptor plays a crucial role in cholesterol metabolism. A related protein, designated the very low density lipoprotein (VLDL) receptor, that specifically binds apolipoprotein (apo) E has recently been characterized and shown to be expressed in heart, muscle and adipose tissue and the human monocyte-macrophage cell line THP-1. The VLDL receptor binds and internalizes VLDL and intermediate density lipoprotein from Watanabe heritable hyperlipidemic (WHHL) rabbits as well as beta-migrating VLDL from cholesterol-fed rabbits but not LDL from WHHL rabbits. Chinese hamster ovary (CHO) cells transfected with the rabbit VLDL receptor cDNA have now been shown to bind or internalize VLDL (d < 1.006 g/ml) isolated from fasted normolipidemic human subjects with lower affinity than WHHL-VLDL or rabbit beta-VLDL. However, binding and internalization were markedly enhanced when fasted human VLDL was preincubated with either recombinant human apoE (3/3) or lipoprotein lipase (LPL) in CHO cells overexpressing the rabbit or human VLDL receptor. CHO cells transfected with both the rabbit VLDL receptor cDNA and the human LPL cDNA effectively bound, internalized, and degraded fasted human VLDL without pretreatment. Treatment of heparinase reduced the effect of LPL-mediated binding at 4 degrees C, but the inhibitory effect was lower at 37 degrees C. Pseudomonas LPL also enhanced the binding of human fasted VLDL to the VLDL receptor at 37 degrees C in CHO cells overexpressing the human VLDL receptor. Taken together, LPL causes the enhancement of triglyceride-rich lipoproteins binding to the VLDL receptor via both the formation of bridge between lipoproteins and heparan sulfate proteoglycans and its lipolytic effect. Ligand blot analysis showed that the apparent molecular mass of the VLDL receptor is 118 kDa, which is smaller than that of the LDL receptor. These results indicate that the VLDL receptor recognizes both triglyceride-rich lipoproteins that are also relatively rich in apoE, as well as the remnants of triglyceride-rich lipoproteins after catabolism and the interaction with heparan sulfate proteoglycans by LPL. The VLDL receptor may thus function as a receptor for remnants of triglyceride-rich lipoproteins in extrahepatic tissues.

Apolipoproteins E↗
PubMed1981

High density lipoprotein subfractions in relation to lipoprotein lipase activity of tissues in man--evidence for reciprocal regulation of HDL2 and HDL3 levels by lipoprotein lipase.

High density lipoprotein subfractions HDL2 and HDL3 were separated from plasma of 22 normolipidemic healthy human subjects and analyzed for cholesterol, triglyceride, phospholipid and protein. In the same subjects the heparin-releasable lipoprotein lipase activity was assayed from biopsies of adipose tissue and skeletal muscle. A significant inverse correlation was found between the plasma concentrations of HDL2 and HDL3 (4= -0.55, p less than 0.01). The HDL2 cholesterol and HDL2 phospholipid levels were negatively correlated with HDL3 protein levels. The total HDL2 and HDL2 cholesterol, phospholipid and protein concentrations were all positively correlated with lipoprotein lipase activity of both adipose tissue and skeletal muscle. In contrast, the corresponding HDL3 values did not show any correlation with adipose tissue lipoprotein lipase but the HDL3 cholesterol, triglyceride and protein levels were inversely correlated with skeletal muscle lipoprotein lipase activity. The results suggest that plasma HDL2 and HDL3 concentrations are reciprocally regulated by the activity of lipoprotein lipase. THe data are compatible with a concept proposing conversion of HDL3 to HDL2 through assimilation of cholesterol, phospholipids and apoproteins from triglyceride-rich lipoproteins during their degradation by lipoprotein lipase. Particularly the concentration of the HDL2 is closely related to the rat of intravascular lipolysis.

Adipose Tissue↗
PubMed1982

Metabolic disorders of serum lipoproteins in endotoxin-poisoned mice: the role of high density lipoprotein (HDL) and triglyceride-rich lipoproteins.

A study was performed to clarify the role of serum lipoproteins, especially high density lipoprotein (HDL) and triglyceride-rich lipoproteins in endotoxemic or endotoxin-poisoned animals. The level of HDL-cholesterol decreased markedly in mouse serum 18-24 hr postintoxication, while the amount of low density lipoprotein (LDL)-cholesterol in the sera of poisoned mice was about 175% of that of the controls. Serum lecithin-cholesterol acyltransferase activity in the poisoned mice decreased slightly for 3-6 hr after endotoxin injection, but became markedly increased at 18-24 hr as compared with that in the controls. The amount of serum very low density lipoprotein (VLDL) showed a marked increase in the poisoned mice 8-24 hr postintoxication. The HDL fraction in the electrophoretic patterns of serum was reduced according to the dose of endotoxin 18 hr postintoxication. The HDL fraction in mice injected with lead acetate plus endotoxin was markedly lower than that in the poisoned mice. When streptozotocin-diabetic mice were injected with endotoxin, the HDL fraction was higher than that in the endotoxin-poisoned mice. In endotoxin-poisoned mice a correlation was observed between the lipid peroxide and LDL levels in the serum. In disk electrophoretic patterns, the HDL fraction in mice given vitamin E-supplemented diet showed a higher level than that in mice given a normal diet. Lipoprotein lipase (LPL) activity in poisoned mice significantly decreased to 59% of the control value 18 hr postintoxication, but hepatic triglyceride lipase activity was only slightly increased in endotoxin-poisoned mice. In analysis of HDL apoprotein peptide in serum lipoprotein, the apo C-II peptide level was clearly lower in mouse serum 18 hr postintoxication than that in the controls. These results suggest that the decrease in LPL activity in endotoxin-poisoned mice may be closely related to a decrease in the apo C-II peptide level, and also that it plays an important part in HDL and triglyceride-rich lipoprotein metabolism in the poisoned mice.

Animals↗
PubMed1995

ELISA quantitation of apolipoproteins in plasma lipoprotein fractions: ApoE in ApoB-containing lipoproteins (Lp B:E) and ApoB in ApoE-containing lipoproteins (Lp E:B).

Growing clinical evidence suggests that metabolic behavior and atherogenic potential vary within lipoprotein subclasses that can be defined by apolipoprotein variation. Variant constituency of apolipoproteins B and E (apoB and apoE) may be particularly important because of the central roles of these apolipoproteins in the endogenous lipid delivery cascade. ApoB is the sole protein of low-density lipoprotein (LDL), and like LDL cholesterol, the plasma apoB level has been positively correlated with risk for atherosclerotic disease. ApoE is a major functional lipoprotein in the triglyceride-rich lipoproteins, and may be crucial in the conversion of very low density lipoprotein (VLDL) to LDL. Based on work by others that enabled the quantititation of apoB-containing particles by content of up to two other types of apolipoprotein, we have developed a method for determining the amount of apoE in apoB-containing lipoproteins (Lp B:E) and the amount of apoB in apoE-containing lipoproteins (Lp E:B). From the Lp B:E and Lp E:B concentrations, the molar ratio of apoE to apoB in lipoproteins containing apoB and/or apoE in plasma can be determined. The methodology is fast, specific, and sensitive and should prove extremely useful in further categorizing lipoproteins and characterizing their behavior. In applying this method to clinical groupings of normo- and hyperlipidemia, we found that the plasma triglyceride level correlated with the apoE and Lp B:E concentrations in plasma, while the total cholesterol level correlated with the apoB and Lp E:B levels.

Antibody Specificity↗
PubMed2004

Ability of non-high-density lipoprotein cholesterol and calculated intermediate-density lipoprotein to identify nontraditional lipoprotein subclass risk factors in dialysis patients.

BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) and calculated intermediate-density lipoprotein cholesterol (IDL-C) have been proposed as surrogate markers to estimate apolipoprotein B-containing lipoproteins. The purpose of this study was to determine the validity of non-HDL-C and calculated IDL-C to predict nontraditional lipoprotein risk factors among dialysis patients and to compare the prevalence of these nontraditional risk factors between dialysis modalities. METHODS: The authors performed a cross-sectional analysis comparing standard lipid profile with lipoprotein analysis via nuclear magnetic resonance (NMR) spectroscopy among 186 hemodialysis (HD) and peritoneal dialysis (PD) patients on modern lipid-lowering therapy. RESULTS: The PD group had a significantly higher low-density lipoprotein (LDL) particle concentration (P < 0.005), higher large very low-density lipoprotein (VLDL; P < 0.001), greater small dense LDL (P < 0.001), and lower protective large HDL (P < 0.005). Forty-six (40%) of 118 subjects with LDL-C below goal had at least 1 nontraditional risk factor by NMR spectroscopy. The sensitivity of non-HDL-C method together with triglyceride (TG) value greater than 200 mg/dL (>2.26 mmol/L) to predict nontraditional risk was 13% and increased to 20% if TG values were excluded. A negative correlation was observed between LDL particle size and HDL-C (r2 = 0.269; P < 0.001); the sensitivity of HDL-C to predict LDL size was 92%. There was no relationship between measured IDL by NMR and calculated IDL-C (r2 = 0.005; P = 0.69). CONCLUSION: Non-HDL-C greater than 130 mg/dL (3.4 mmol/L) independent of TG values and HDL-C lower than 40 mg/dL (1.0 mmol/L) may predict nontraditional lipoprotein risk factors among dialysis patients. This is especially applicable to patients on PD, a modality associated with a more atherogenic lipoprotein profile.

Aged↗