Biomedical subjects

A Chait

Publications and source records attributed to A Chait.

At least 109 records · Page 6Linked to original sources

PubMed1989

Direct evidence for a protein recognized by a monoclonal antibody against oxidatively modified LDL in atherosclerotic lesions from a Watanabe heritable hyperlipidemic rabbit.

Low density lipoproteins (LDL) that have been oxidatively modified have been implicated in the pathogenesis of atherosclerosis. Monoclonal antibodies were generated against oxidatively modified human low density lipoproteins (OxLDL); these antibodies reacted with OxLDL, but did not react with native LDL, either in an enzyme-linked immunosorbent assay (ELISA) or a Western blot analysis. The anti-OxLDL antibodies did react with other modified forms of LDL (eg, acetylated LDL, malondialdehyde-modified LDL, and cell-modified LDL) that were recognized by the scavenger receptor on macrophages. Single- and double-label immunofluorescence of atheromatous lesions from a Watanabe heritable hyperlipidemic (WHHL) rabbit demonstrated some colocalization of proteins detected by anti-LDL and anti-OxLDL antibodies. However, clearly there were also areas stained by the anti-OxLDL antibodies that did not stain with anti-LDL. Staining of the lesion by the anti-OxLDL antibody was abolished by adsorption of the antibody with OxLDL, but not by adsorption with LDL or bovine serum albumin. Arterial tissue from a control New Zealand White rabbit did not show staining with anti-LDL or anti-OxLDL antibodies. These observations suggest that OxLDL (or possibly other proteins recognized by the anti-OxLDL antibody) is present in atheromatous lesions of WHHL rabbits, and are consistent with oxidatively modified lipoproteins having a role in atherogenesis.

Animals↗

PubMed1989

Loss of copper-zinc superoxide dismutase gene expression in differentiated cells of myelo-monocytic origin.

Changes in the production of reactive oxygen species and total superoxide dismutase activity have been observed during differentiation of some hematopoietic cells. We therefore investigated whether the steady-state level and rate of transcription of superoxide dismutase-1 (SOD-1) mRNA change during terminal differentiation of the human leukemia cell lines THP-1, HEL, and HL-60 into macrophages and/or granulocytes, respectively. Macrophage differentiation is accompanied by a gradual decrease in both the transcription rate (10x) and the steady-state level (6x) of SOD-1 mRNA. No decrease was observed after treatment with the diacylglycerol analog 1,2 dioctanol-rac-glycerol (di-C8), which like phorbol 12-myristate 13-acetate also activates protein kinase C but does not induce differentiation at the concentration used. The same decrease in SOD-1 mRNA level was observed when HL-60 cells were induced to differentiate into granulocytes by treatment with dimethylsulfoxide. These data suggest that a decrease in SOD-1 mRNA to almost undetectable levels accompanies differentiation of macrophages and granulocytes.

Cell Differentiation↗

PubMed1989

Hepatoportal arteriovenous fistula treated with detachable balloon embolotherapy.

Hepatic artery to portal vain fistulas were first reported in 1892. Symptoms of portal hypertension usually occur within weeks to months, once the fistula develops. Various attempts at surgical occlusion and embolization, with varying results, have been reported. This report is of a 33-yr-old woman who, 23 yrs after an automobile accident, was admitted with ascites and diagnosed as having a right hepatic artery-to-portal vein fistula (RHAPVF), which was successfully occluded via detachable balloon embolic therapy. The ascites resolved within 3 days of the embolotherapy, and subsequent follow-up revealed no recurrence of ascites during the next 18 months.

Adult↗

PubMed1988

The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells.

To study the effect of triglyceride content of low density lipoprotein (LDL) on its physicochemical and biological properties, we have depleted the triglyceride by incubation with hepatic lipase (HL-LDL) and raised the triglyceride by incubation of HL-LDL with very low density lipoprotein and lipoprotein-deficient serum. HL-LDL was taken up by human monocyte-derived macrophages and by human skin fibroblasts at an increased rate compared to untreated LDL. Incubation of the various LDL preparations revealed that cellular LDL degradation as well as LDL-mediated cholesterol esterification were inversely related to the triglyceride content of the LDL preparation. Modification of the triglyceride content of LDL also was associated with changes in the free fatty acid content, but the interaction of the LDL with cells was unaffected by the level of this component. The triglyceride content of LDL was found to be reciprocally related to the number of free lysine amino groups of LDL apolipoprotein B (apoB) which could be labeled with trinitrobenzenesulfonic acid. 13C-Nuclear magnetic resonance (NMR) spectra of native LDL and HL-LDL samples containing [13CH3]2 lysine residues formed by reductive methylation (11-13% modification) showed that the arrangement of apoB lysines is perturbed by the exposure to hepatic lipase. The ratio of labeled lysines with pK 8.9 to those with pK 10.5 exposed on the surface of LDL particles was decreased by about 40% by lipase treatment. These effects are apparently due to changes in local apoB conformation because circular dichroism spectra revealed that the average secondary structure of the entire apoB molecule is the same in native LDL and HL-LDL. The triglyceride content of LDL reciprocally affected its binding to a monoclonal antibody which recognizes epitopes around the LDL receptor binding domain of apoB. The above evidence indicates that modulation of the core triglyceride and possibly also surface phospholipid content of LDL can alter the conformation of apoB on the surface of the particle, thereby influencing the interaction with cell surface LDL receptors.

Apolipoprotein B-100↗

PubMed1988

Modification of low density lipoprotein by lipoprotein lipase or hepatic lipase induces enhanced uptake and cholesterol accumulation in cells.

Incubation of low density lipoprotein(s) (LDL) with either lipoprotein lipase or hepatic lipase led to modification of the core lipid composition of LDL. Both lipases modified LDL by substantially reducing core triglyceride content without producing marked differences in size, charge, or lipid peroxide content in comparison to native LDL. The triglyceride-depleted forms of LDL that result from treatment with these two enzymes were degraded at approximately twice the rate of native LDL by human monocyte-derived macrophages (HMDM). Lipase-modified LDL degradation was inhibited by chloroquine, suggesting lysosomal involvement in LDL cellular processing. The increased degradation by macrophages of the LDL modified by these lipases was accompanied by enhanced cholesterol esterification rates, as well as by an increase in cellular free and esterified cholesterol content. In a patient with hepatic triglyceride lipase deficiency, degradation of the triglyceride-rich LDL by HMDM was approximately half that of normal LDL. Following in vitro incubation of LDL from this patient with either lipoprotein or hepatic lipase, lipoprotein degradation increased to normal. Several lines of evidence indicate that LDL modified by both lipases were taken up by the LDL receptor and not by the scavenger receptor. 1) The degradation of lipase-modified LDL in nonphagocytic cells (human skin fibroblast and arterial smooth muscle cells) as well as in phagocytic cells (HMDM, J-774, HL-60, and U-937 cell lines) could be dissociated from that of acetylated LDL and was always higher than that of native LDL. A similar pattern was found for cellular cholesterol esterification and cholesterol mass. 2) LDL receptor-negative fibroblasts did not degrade lipase-modified LDL. 3) A monoclonal antibody to the LDL receptor inhibited macrophage degradation of the lipase-modified LDL. 4) Excess amounts of unlabeled LDL competed substantially with 125I-labeled lipase-modified LDL for degradation by both macrophages and fibroblasts. Thus, lipase-modified LDL can cause significant cholesterol accumulation in macrophages even though it is taken up by LDL and not by the scavenger receptor. This effect could possibly be related to the reduced triglyceride content in the core of LDL, which may alter presentation of the LDL receptor-binding domain of apolipoprotein B on the particle surface, thereby leading to increased recognition and cellular uptake via the LDL receptor pathway.

Antibodies, Monoclonal↗

PubMed1988

Stimulation of receptor-dependent and receptor-independent pathways of low-density lipoprotein degradation in arterial smooth muscle cells by platelet-derived growth factor.

Platelet-derived growth factor (PDGF), a powerful mitogen released by platelets, promoted the degradation of low-density lipoprotein (LDL) by cultured primate arterial smooth muscle cells and human skin fibroblasts by stimulating both receptor-mediated and LDL-receptor-independent uptake of LDL. Stimulation of LDL-receptor-independent LDL uptake and degradation by PDGF was demonstrated in three ways. First, the small amount of LDL that was degraded by LDL-receptor-negative skin fibroblasts was stimulated by PDGF. Second, PDGF led to increased degradation of LDL that had been reductively methylated to prevent its binding to LDL receptors. Third, 125I-labeled LDL degradation was stimulated by PDGF in the presence of high concentrations of unlabeled LDL, i.e., conditions under which the contribution of the LDL receptor to cellular uptake and degradation is reduced. These observations suggest that mitogens, as typified by PDGF, can facilitate the cellular delivery of LDL cholesterol by both LDL-receptor-mediated and non-LDL-receptor-mediated mechanisms to provide exogenous cholesterol for use during cell replication.

Animals↗

PubMed1988

Transcriptional activation of the lipoprotein lipase and apolipoprotein E genes accompanies differentiation in some human macrophage-like cell lines.

Stimulation of the macrophage-like cell line THP-1 with the phorbol ester phorbol 12-myristate 13-acetate (PMA) resulted in differentiation into cells with many features of macrophages. This differentiation was accompanied by transcriptional activation of the lipoprotein lipase (LPL) and apo E genes and accumulation of their protein products in the media. PMA-induced differentiation of the HEL and HL-60 cell lines was not accompanied by induction of the gene for LPL, whereas the apo E gene was induced slightly in HL-60 cells. By contrast, the gene for superoxide dismutase (SOD-1) was either unaffected (THP-1) or down regulated (HL-60 or HEL cells) by PMA treatment. Induction of LPL mRNA in THP-1 cells was dependent upon the concentration of phorbol ester added. A minimal concentration of 1.6 x 10(-8) M PMA was necessary for macrophage differentiation, induction of LPL mRNA, and synthesis of the enzyme. LPL mRNA accumulates within 3 h after stimulation with PMA and attains a maximum concentration after 6 h, thereafter slowly decreasing over the next 3 days. In contrast, the steady-state level of apo E mRNA in the same THP-1 cultures increased gradually over a period of 48 h after induction. These studies thus demonstrate that THP-1 cells are of value as a model to study the quantitative and temporal expression of the LPL and apo E genes during macrophage differentiation.

Apolipoproteins E↗

PubMed1988

Mineral loss in the parenteral nutrition patient.

The impact of parenteral nutrition on mineral loss was examined in 11 long-term (10-79 mo) and 6 short-term (1-8 mo) patients. In the long-term patients, there was a significant (p less than or equal to 0.02) urinary loss of calcium and magnesium during infusion compared with periods off infusion. The magnitude of urinary excretion of these minerals was much lower than in previously reported series and in short-term patients. Despite this, in long-term patients the mean bone mass at the spine was lower than normal (p less than 0.001) but mean bone mass at the wrist was not. Current data suggest that hypercalciuria is not a consistent feature of parenteral nutrition. Furthermore, osteopenia is a feature of some long-term parenteral nutrition patients.

Adult↗

PubMed1988

Annular protrusion: pathophysiology and roentgenographic appearance.

The degenerative changes of the lumbar spine in 100 patients with symptomatic low-back pain were reviewed using plain roentgenograms and computed tomographic scans in order to determine the relationship between degeneration and annular protrusion. Additionally, the lumbar spinal units of 25 fresh cadavers were roentgenographed, injected with a mixture of methylene blue and renografin-60, dissected, and studied. The state of degeneration of each of the intervertebral units of both groups was graded on a four-point scale based on the roentgenographic presence or absence of osteophytes and facet joint changes, and the intervertebral disc height. The degree of annular protrusion was measured by dividing the anteroposterior diameter of the intervertebral disc by the anteroposterior diameter of the vertebral plate as determined on the radiographic studies. In the clinical group, 39 intervertebral discs having Grade II and III degeneration exhibited a statistically higher annular/vertebral diameter ratio (A/V index) of 1.30 as compared to the normal invertebral discs, with an A/V index of 1.12 (P less than 0.001). The dissection of the disc spaces of the cadavers with radiographic evidence of disc space narrowing and marginal osteophytosis, Grade II and III degeneration, displayed significant interruption and tearing of the annular fibers and peripheral migration of collagenized nuclear fragments. In both the clinical and pathologic groups, there was a direct correlation between the size of the annular bulge, as indicated in the A/V index, and the degree of narrowing of the disc space. Therefore, this study indicated that annular protrusion is an intricate part of the degeneration process.

Adult↗

PubMed1988

Bacterial lipopolysaccharide reduces macrophage lipoprotein lipase levels: an effect that is independent of tumor necrosis factor.

Human monocyte-derived macrophages secrete lipoprotein lipase (LPL) in culture. The regulation of human macrophage LPL production is poorly understood. Since bacterial lipopolysaccharide (LPS) alters production of several macrophage secretory products, its effect on human monocyte-derived macrophage LPL was tested. LPS treatment produced a dramatic dose-dependent decrease in LPL activity in macrophage-conditioned media. At 100 ng/ml LPS, medium LPL activity dropped by 60%. The effect of LPS on macrophage LPL activity was rapid, was blocked by polymixin B, and was not due to cytotoxicity. LPS lowers (by about 60%) the steady state level of LPL mRNA, suggesting that its effect is exerted at the level of mRNA metabolism. Since LPS stimulates macrophage production of cachectin/tumor necrosis factor (TNF), a potent inhibitor of LPL production by the 3T3-L1 adipocyte-like cell line, it was determined whether TNF reduces macrophage LPL levels. Treatment of human macrophages with up to 1000 U/ml of recombinant human TNF had no effect on macrophage LPL activity. When TNF was added in combination with LPS, no additional effect on LPL activity was observed over that seen with LPS alone. Furthermore, the LPS effect was not blocked by a monoclonal anti-TNF antibody. Thus, bacterial LPS potently decreases macrophage LPL activity and mass independent of an autocrine effect of TNF.

Arteriosclerosis↗

PubMed1987

The role of sulfur-containing amino acids in superoxide production and modification of low density lipoprotein by arterial smooth muscle cells.

Extracellular superoxide (O2-.) was detected in cultures of monkey arterial smooth muscle cells as measured by the superoxide dismutase-inhibitable reduction of cytochrome c and acetylated cytochrome c. Reduction of cytochrome c by these cells required L-cystine in the incubation medium. A variety of other sulfur-containing amino acids, including D-cystine, L-cystathionine, L-methionine, and djenkolic acid did not support O2-. generation when present at concentrations equimolar to L-cystine. At millimolar concentrations, the chelators EDTA and diethylene triamine penta-acetic acid inhibited O2-. production by smooth muscle cells. This effect was maximal when the chelator was present at the same concentration as the sum of the Ca2+ and Mg2+ in the medium, suggesting a role for these cations in O2-. generation by cells. Modification of low density lipoprotein (LDL) by arterial smooth muscle cells, as assessed by changes in lipid peroxide content, mobility on agarose gel electrophoresis, and apoprotein B fragmentation, was also L-cystine-dependent. LDL modification also required micromolar concentrations of the transition metal ion Cu(II) or Fe(III) and was inhibited by superoxide dismutase. LDL modified by smooth muscle cells in the presence of L-cystine and Cu(II) was taken up and degraded less well than native LDL by human skin fibroblasts, suggesting that recognition by the LDL receptor was lost. In contrast, LDL modified by smooth muscle cells was taken up and degraded to a greater degree than native LDL by mouse peritoneal macrophages, consistent with recognition by the scavenger receptor. These results indicate that monkey arterial smooth muscle cells produce O2-. and modify LDL by an L-cystine-dependent process. This may involve reduction of cystine to a thiol, possibly cysteine or a cysteine-containing peptide such as glutathione. Sulfur-containing amino acids may play a role in atherogenesis by supporting cell-mediated generation of reactive oxygen species and modification of lipoprotein to a form recognized by the scavenger receptor.

Amino Acids, Sulfur↗

PubMed1987

Metabolic consequences of genetic heterogeneity of lipoprotein composition (lipoprotein heterogeneity).

Lipoprotein composition varies among different genetic forms of hyperlipidemia. An increase in hepatic triglyceride (TG) synthesis in subjects with familial hypertriglyceridemia (FHTG) is associated with secretion of large, TG-enriched, very low-density lipoproteins (VLDL), which have an increased affinity for lipoprotein lipase (LPL) in vivo as compared with VLDL from subjects with familial combined hyperlipidemia (FCHL) or from normal subjects. Elevated levels of plasma low-density lipoprotein (LDL) apoprotein B in FCHL are associated with high apoprotein B production rates. The LDL in FCHL is heterogeneous, with a preponderance of an LDL subfraction, which is denser, smaller, and lipid poor as compared with LDL from normal subjects. The more buoyant LDL subfraction in FCHL seems to be catabolized more rapidly than this dense LDL subfraction.

Apolipoproteins B↗

PubMed1987

Progression of atherosclerosis: the cell biology.

The sequence of events during atherogenesis has been deduced from serial changes that occur in animal models of atherosclerosis and from autopsy studies in humans. In vitro studies have provided insight into the mechanisms of the major features of atherosclerosis. One of the earliest events in atherogenesis is adhesion of monocytes to intact endothelium, followed by migration along a chemotactic gradient into the intima, where they become macrophages. These events appear to be modulated by lipoproteins. Subendothelial macrophages accumulate cholesteryl ester and become the foam cells of the fatty streak. Smooth muscle cells proliferate in response to stimulation by mitogens. Later, intimal macrophages and smooth muscle cells also accumulate lipid, by apparently different mechanisms. Later, lipoproteins accumulate in the extracellular space where they are bound to proteoglycans. Strategies to prevent atherosclerosis should be targeted towards specific events in the cell biology of this disease.

Animals↗

PubMed1986

Evidence for kinetic heterogeneity among human low density lipoproteins.

The kinetics of low density lipoprotein apolipoprotein B (LDL apo B) metabolism are usually determined using turnover techniques in which radioiodinated LDL apo B is injected as a bolus into plasma, and serial plasma and urinary radioactivity samples are taken. The metabolic parameter of interest usually estimated from such data is the fractional catabolic rate (FCR). Two methods are normally employed to obtain an estimate of the FCR. One, the so-called Matthews' analysis, assumes plasma LDL apo B metabolism can be described by a single plasma pool while the other is determined by calculating the ratio of urinary radioactivity excreted to mean plasma radioactivity per day. Both of these methods assume LDL apo B is kinetically homogeneous, thus ignoring the evidence that LDL is biochemically heterogeneous in some individuals. If this biochemical heterogeneity manifests itself as kinetic heterogeneity, then the use of these data to estimate the FCR will not permit the resolution of the finer details of potential metabolic defects. This paper addresses the question of kinetic homogeneity and heterogeneity of LDL apo B within the context of several integrated kinetic models of increasing complexity. Each model fits reasonably the turnover data and hence cannot be rejected on the basis of failure to be compatible with the data. However, the models have strikingly different physiologic interpretations while providing essentially the same estimate for the FCR. Thus LDL apo B metabolism appears to be more complex than originally believed, and the models provide a framework within which to design new experiments to distinguish among them.

Adult↗

PubMed1986

Low density lipoprotein metabolism in familial combined hyperlipidemia and familial hypercholesterolemia: kinetic analysis using an integrated model.

Several models for low density lipoprotein (LDL) apo B metabolism were applied to LDL turnover data from subjects with two distinct genetic forms of hyperlipidemia, familial hypercholesterolemia (FH), and familial combined hyperlipidemia (FCHL). Of the first two models tested, there was good agreement between the observed and predicted data for FH in one (model A), and for FCHL in the other (model B). The major difference between these two models is that LDL is kinetically homogeneous in model A and heterogeneous in model B, raising the possibility that LDL subspecies differences may occur between these two disorders. The findings are consistent with LDL homogeneity in FH and LDL heterogeneity in FCHL. Two other integrated models (models C and D) provided good agreement between observed and predicted data in both disorders. Although neither could be rejected outright on the basis of known physiology, parameter estimates were more variable with model D. Analysis of the data using model C was consistent with the known pathophysiologic defect in LDL catabolism in FH and suggests that individuals with FH as well as FCHL have more than one LDL subpopulation in plasma. The urine/plasma (U/P) ratio was shown to be constant from day 4 to day 14 of the study in FH, while in FCHL this value declined in all cases. Thus, determination of LDL fractional catabolic rates (FCR) by the U/P ratio method may be invalid in certain groups of patients. The other traditional method for calculating LDL FCR, the Matthews' analysis, overestimated FCR in some instances, and could lead to systematic errors when used to determine LDL FCR and production rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells.

Extracellular superoxide was detected in cultures of monkey and human arterial smooth muscle cells as indicated by superoxide dismutase inhibitable reduction of cytochrome c. Superoxide production by these cells in the presence of Fe or Cu resulted in modification of low density lipoprotein (LDL). The degree of LDL modification was directly proportional to the rate of superoxide production by cells. Superoxide dismutase (100 micrograms/ml), and the general free radical scavengers butylated hydroxytoluene and butylated hydroxyanisole (50 microM), inhibited Fe- and Cu-mediated modification of LDL by monkey smooth muscle cells, while catalase (100 micrograms/ml) and mannitol (25 mM) had no effect. The chelators desferrioxamine and diethylenetriamine pentaacetic acid completely inhibited Fe- and Cu-promoted modification of LDL, while EGTA had no inhibitory effect. EDTA stimulated Fe-promoted modification in the 1-100 microM range while inhibiting Cu-mediated modification of LDL. LDL modified by smooth muscle cells in the presence of 10 microM Fe or Cu stimulated [14C]oleate incorporation into cholesteryl ester by human macrophages and murine J774 cells to a degree comparable to that produced by acetylated LDL. LDL incubated with smooth muscle cells and metal ions in the presence of superoxide dismutase failed to enhance macrophage cholesteryl ester accumulation. Thus, arterial smooth muscle cells in culture generate superoxide and modify LDL by a superoxide-dependent, Fe or Cu catalyzed free radical process, resulting in enhanced uptake of the modified LDL by macrophages. Neither hydroxyl radicals nor H2O2 are likely to be involved. Superoxide-dependent lipid peroxidation may contribute to biological modification of LDL, resulting in foam cell formation and atherogenesis.

Animals↗

PubMed1985

Secretion of a lipid transfer protein by human monocyte-derived macrophages.

Human monocyte-derived macrophages in culture were shown to synthesize and secrete a lipid transfer protein. The human monocyte-derived macrophage transfer protein showed the following characteristics: (i) linear secretion rate over a 24-h period, which was blocked completely by cycloheximide and stimulated by phorbol myristate acetate (67% increase over nonstimulated values); (ii) apparent Mr = approximately 62,000 off Sephacryl S-200; (iii) isoelectric point of 5.0; (iv) binding to phenyl-Sepharose, but not to heparin-Sepharose; (v) facilitation of the transfer of both neutral lipids (cholesteryl esters and triglycerides) and phosphatidylcholine between high density lipoproteins and d less than 1.063 g/ml lipoproteins; and (vi) thermal stability (stable for 1 h at 56 degrees C). The last five of these properties are similar to those of the plasma lipid transfer protein. Thus, macrophages secrete a lipid transfer protein that closely resembles the neutral lipid transfer protein found in human plasma and may be a source of this plasma protein in vivo.

Carrier Proteins↗

PubMed1985

Metabolism of low-density lipoprotein from patients with diabetic hypertriglyceridemia by cultured human skin fibroblasts.

To test whether triglyceride-enriched low-density lipoprotein (LDL) obtained from subjects with diabetic hypertriglyceridemia is metabolized normally by cells, LDL was separated from seven healthy control subjects (fasting plasma glucose [FPG] 91 +/- 10 mg/dl [mean +/- SD], triglyceride [TG] 110 +/- 47 mg/dl), six diabetic normolipidemic patients (FPG 218 +/- 65 mg/dl; TG 139 +/- 75 mg/dl), six diabetic hypertriglyceridemic patients (FPG 214 +/- 71 mg/dl; TG 1915 +/- 1680 mg/dl), and five nondiabetic hypertriglyceridemic patients (FPG 92 +/- 8 mg/dl; TG 2013 +/- 1889 mg/dl). Binding of 125I-labeled LDL from hypertriglyceridemic subjects with and without diabetes to cultured skin fibroblasts was significantly decreased to 74 +/- 19% and 78 +/- 14% of that seen with LDL from normolipidemic nondiabetic subjects and diabetic normolipidemic controls (100 +/- 0%, 101 +/- 25%; P less than 0.005). Unlabeled LDL from hypertriglyceridemic subjects with and without diabetes failed to suppress LDL receptor activity and sterol synthesis from 14C-acetate as efficiently as unlabeled LDL from healthy subjects. The ability of LDL from hypertriglyceridemic subjects, whether diabetic or not, to suppress LDL binding was inversely related to the ratio of triglyceride to protein in LDL (r = 0.71, P less than 0.01) and showed a positive correlation with the LDL cholesterol/protein ratio (0.69, P less than 0.01). Thus, LDL from patients with hypertriglyceridemia, with or without coexistent diabetes, shows impaired binding to LDL receptors and less ability to downregulate LDL receptor activity and sterol synthesis than does LDL from normolipidemic diabetic and nondiabetic subjects. These findings suggest that factors associated with hypertriglyceridemia rather than with diabetes result in altered metabolism of LDL in these disorders.

Adult↗