Total cholesterol,low density lipoprotein cholesterol,and high density lipoprotein cholesterol and coronary heart disease in Scotland.

OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION--Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes.     

Concentrations of high density lipoprotein cholesterol,triglycerides, and total cholesterol in ischaemic heart disease.

OBJECTIVE--To assess the roles of serum concentrations of total cholesterol, high density lipoprotein cholesterol, and triglycerides in predicting major ischaemic heart disease. DESIGN--Men recruited for the British regional heart study followed up for a mean of 7.5 years. SETTING--General practices in 24 British towns. PATIENTS--7735 Middle aged men. END POINT--Predictive value of serum concentrations of lipids. MEASUREMENTS AND MAIN RESULTS--At initial screening serum concentrations of total cholesterol, high density lipoprotein cholesterol, and triglycerides were determined from non-fasting blood samples. Altogether 443 major ischaemic heart disease events (fatal and non-fatal) occurred during the study. Men in the highest fifth of the distribution of total cholesterol concentration (greater than or equal to 7.2 mmol/l) had 3.5 times the risk of ischaemic heart disease than did men in the lowest fifth (less than 5.5 mmol/l) after adjustment for high density lipoprotein cholesterol concentration and other risk factors. Men in the lowest fifth of high density lipoprotein cholesterol concentration (less than 0.93 mmol/l) had 2.0 times the risk of men in the highest fifth (greater than or equal to 1.33 mmol/l) after adjustment for total cholesterol concentration and other risk factors. Men in the highest fifth of triglyceride concentration (greater than or equal to 2.8 mmol/l) had only 1.3 times the risk of those in the lowest fifth (less than 1.08 mmol/l) after adjustment for total cholesterol concentration and other risk factors; additional adjustment for high density lipoprotein cholesterol concentration made the association with ischaemic heart disease disappear. CONCLUSIONS--Serum concentration of total cholesterol is the most important single blood lipid risk factor for ischaemic heart disease in men. High density lipoprotein cholesterol concentration is less important, and triglyceride concentrations do not have predictive importance once other risk factors have been taken into account.     

Alcohol consumption,serum low density lipoprotein cholesterol concentration,and risk of ischaemic heart disease: six year follow up in the Copenhagen male study.

OBJECTIVES: To investigate the interplay between use of alcohol, concentration of low density lipoprotein cholesterol, and risk of ischaemic heart disease. DESIGN: Prospective study with controlling for several relevant confounders, including concentrations of other lipid fractions. SETTING: Copenhagen male study, Denmark. SUBJECTS: 2826 men aged 53-74 years without overt ischaemic heart disease. MAIN OUTCOME MEASURE: Incidence of ischaemic heart disease during a six year follow up period. RESULTS: 172 men (6.1%) had a first ischaemic heart disease event. There was an overall inverse association between alcohol intake and risk of ischaemic heart disease. The association was highly dependent on concentration of low density lipoprotein cholesterol. In men with a high concentration (> or = 5.25 mmol/l) cumulative incidence rates of ischaemic heart disease were 16.4% for abstainers, 8.7% for those who drank 1-21 beverages a week, and 4.4% for those who drank 22 or more beverages a week. With abstainers as reference and after adjustment for confounders, corresponding relative risks (95% confidence interval) were 0.4 (0.2 to 1.0; P<0.05) and 0.2 (0.1 to 0.8; P<0.01). In men with a concentration <3.63 mmol/l use of alcohol was not associated with risk. The attributable risk (95% confidence interval) of ischaemic heart disease among men with concentrations > or = 3.63 mmol/l who abstained from drinking alcohol was 43% (10% to 64%). CONCLUSIONS: In middle aged and elderly men the inverse association between alcohol consumption and risk of ischaemic heart disease is highly dependent on the concentration of low density lipoprotein cholesterol. These results support the suggestion that use of alcohol may in part explain the French paradox.     

Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies

Objective To explore the association between migraine and risk of ischaemic stroke.Design Systematic review and meta-analysis.Data sources Observational studies published between 1966 and June 2004 (identified through Medline and Embase) that examined the association between migraine and risk of ischaemic stroke.Results 14 studies (11 case-control studies and 3 cohort studies) were identified. These studies suggest that the risk of stroke is increased in people with migraine (relative risk 2.16, 95% confidence interval 1.89 to 2.48). This increase in risk was consistent in people who had migraine with aura (relative risk 2.27, 1.61 to 3.19) and migraine without aura (relative risk 1.83, 1.06 to 3.15), as well as in those taking oral contraceptives (relative risk 8.72, 5.05 to 15.05).Conclusions Data from observational studies suggest that migraine may be a risk factor in developing stroke. More studies are needed to explore the mechanism of this potential association. In addition, the risk of migraine among users of oral contraceptives must be further investigated.     

Effects of lipoprotein lipase and statins on cholesterol uptake into heart and skeletal muscle

Regulation of cholesterol metabolism in cultured cells and in the liver is dependent on actions of the LDL receptor. However, nonhepatic tissues have multiple pathways of cholesterol uptake. One possible pathway is mediated by LPL, an enzyme that primarily hydrolyzes plasma triglyceride into fatty acids. In this study, LDL uptake and tissue cholesterol levels in heart and skeletal muscle of wild-type and transgenic mice with alterations in LPL expression were assessed. Overexpression of a myocyte-anchored form of LPL in heart muscle led to increased uptake of LDL and greater heart cholesterol levels. Loss of LDL receptors did not alter LDL uptake into heart or skeletal muscle. To induce LDL receptors, mice were treated with simvastatin. Statin treatment increased LDL receptor expression and LDL uptake by liver and skeletal muscle but not heart muscle. Plasma creatinine phosphokinase as well as muscle mitochondria, cholesterol, and lipid droplet levels were increased in statin-treated mice overexpressing LPL in skeletal muscle. Thus, pathways affecting cholesterol balance in heart and skeletal muscle differ.     

Why Londoners have low death rates from ischaemic heart disease and stroke.

OBJECTIVE--To explain the low death rates from cardiovascular disease in London. SETTING--London and the other counties of England and Wales. SUBJECTS--Women living in London during 1901-10 and people in London dying during 1968-78. RESULTS--At the beginning of the twentieth century young women aged 15-34 in London had remarkably low death rates, largely because of low rates for tuberculosis and other infectious diseases and low mortality during childbirth. Their low death rates contrasted with the high rates in girls under 15 years. CONCLUSIONS--Large numbers of young women had migrated into London from agricultural counties in southern England and went into domestic service, where the diet was usually very good. Recent findings suggest that a mother''s nutrition and health has a major effect on the risk of cardiovascular disease in the next generation. The low cardiovascular mortality in London is consistent with this, and contrasts with the high mortality from other common diseases.     

Differences in the metabolism of oxidatively modified low density lipoprotein and acetylated low density lipoprotein by human endothelial cells: inhibition of cholesterol esterification by oxidatively modified low density lipoprotein

The rate of degradation of oxidatively modified low density lipoprotein (Ox-LDL) by human endothelial cells was similar to that of unmodified low density lipoprotein (LDL), and was approximately 2-fold greater than the rate of degradation of acetylated LDL (Ac-LDL). While LDL and Ac-LDL both stimulated cholesterol esterification in endothelial cells, Ox-LDL inhibited cholesterol esterification by 34%, demonstrating a dissociation between the degradation of Ox-LDL and its ability to stimulate cholesterol esterification. Further, while LDL and Ac-LDL resulted in a 5- and 15-fold increase in cholesteryl ester accumulation, respectively, Ox-LDL caused only a 1.3-fold increase in cholesteryl ester mass. These differences could be accounted for, in part, by the reduced cholesteryl ester content of Ox-LDL. However, when endothelial cells were incubated with Ac-LDL in the presence and absence of Ox-LDL, Ox-LDL led to a dose-dependent inhibition of cholesterol esterification without affecting the degradation of Ac-LDL. This inhibitory effect of Ox-LDL on cholesteryl ester synthesis was also manifest in normal human skin fibroblasts incubated with LDL and in LDL-receptor-negative fibroblasts incubated with unesterified cholesterol to stimulate cholesterol esterification. Further, the lipid extract from Ox-LDL inhibited cholesterol esterification in LDL-receptor negative fibroblasts. These findings suggest that the inhibition of cholesterol esterification by oxidized LDL is independent of the LDL and scavenger receptors and may be a result of translocation of a lipid component of oxidatively modified LDL across the cell membrane.     

Utilization of very low density lipoprotein by rat heart: the effect of endotoxin

The effect of endotoxin on myocardial utilization of very low density lipoprotein (VLDL) triacylglycerol (TAG) was studied. VLDL was prepared by rat liver perfusion and tested as substrate in the isolated working rat heart. Both liver and heart donor rats were pretreated in vivo with endotoxin or vehicle (control). VLDL-TAG synthesized by endotoxin-pretreated livers was assimilated and oxidized at an increased rate by hearts compared with control VLDL-TAG, regardless of the cardiac endotoxic status, with increased cardiac mechanical performance (cardiac output, hydraulic work). There was no change in incorporation of labeled VLDL lipids into myocardial tissue lipids. Lipoprotein lipase (LPL) activity was increased in endotoxin-pretreated hearts, and after perfusion with "endotoxic" VLDL, there was a tendency for translocation of LPL from tissue-residual to heparin-releasable compartments, but these changes were modest. Analysis of the VLDL composition showed that endotoxin-pretreated livers produced apolipoprotein (apo)-B48 VLDL with decreased particle size (and hence TAG content), but apo-B100 VLDL was unchanged. Oleate content of VLDL was increased, but there was no difference in apo-C or apo-E content. These results suggest that VLDL-TAG produced during sepsis/endotoxinemia may be destined for utilization by the heart as energy substrate. However, the mechanism for its increased efficacy is uncertain.     

Sialic acid content of low density lipoprotein and its relation to lipid concentrations and metabolism of low density lipoprotein and cholesterol

A low sialic acid content in low density lipoprotein (LDL) has been associated with atherogenicity and coronary artery disease (CAD) in many but not all studies. We investigated associations of the sialic acid-to-apolipoprotein B (apoB) ratio of LDL with lipoprotein lipid concentrations, kinetics of LDL, metabolism of cholesterol, and the presence of CAD in 98 subjects (CAD(+), n = 56; CAD(-), n = 42). The sialic acid ratios of total, dense, and very dense LDL were lower in the CAD(+) than CAD(-) subjects, especially at high sialic acid ratios. The LDL sialic acid ratio was inversely associated with respective lipid and apoB concentrations and positively with lipid-to-apoB ratios of LDL. The transport rates (TRs) for total and dense LDL apoB were negatively associated with their sialic acid ratios. The sialic acid ratio of dense LDL, but not that of total LDL, was inversely correlated with serum levels of cholesterol precursor sterols, indicators of cholesterol synthesis, and positively with serum levels of plant sterols, indicators of cholesterol absorption. In addition, the TR for dense LDL was positively correlated with cholesterol synthesis.In conclusion, a low LDL sialic acid ratio was associated with CAD, high numbers of small LDL particles, and a high TR for LDL apoB, and in dense LDL also with high synthesis and low absorption of cholesterol.     

Reconciling the evidence on serum homocysteine and ischaemic heart disease: a meta-analysis

Background

Results from genetic epidemiological studies suggest that raised serum homocysteine is a cause of ischaemic heart disease, but the results of randomised trials suggest otherwise. We aimed to update meta-analyses on each type of study using the latest published data and test a hypothesis based on antiplatelet therapy use in the trials to explain the discrepancy.

Methods and Findings

Meta-analyses of ischaemic heart disease using (i) 75 studies in which the prevalence of a mutation (CT) in the MTHFR gene (which increases homocysteine) was determined in cases (22,068) and controls (23,618), and (ii) 14 randomised trials (39,597 participants) of homocysteine lowering and ischaemic heart disease events. The summary estimates from the two analyses were compared. Meta-analysis of the MTHFR studies showed a statistically significantly increased risk of ischaemic heart disease in TT compared with CC homozygotes; odds ratio 1.16 (1.04 to 1.29) for a 1.9 µmol/L homocysteine difference (TT minus CC). Meta-analysis of randomised trials showed no significant reduction in IHD risk from folic acid; relative risk 1.00 (0.93 to 1.08), despite a reduction in homocysteine of 3.3 µmol/L. There was a statistically significant difference in risk reduction between the 5 trials with the lowest prevalence of antiplatelet therapy (60% on average, usually aspirin), RR 0.93 (0.84 to 1.05) and the 5 trials with the highest prevalence (91% on average), RR 1.09 (1.00 to 1.19), p = 0.037 for the difference.

Conclusion

Discordant results from MTHFR studies and randomised trials could be explained by aspirin reducing or negating the anti-platelet effect of lowering homocysteine. On this basis, folic acid would have a role in the primary prevention of ischaemic heart disease, when aspirin is not taken routinely, but not in secondary prevention, when it is routine.     

Thymus fraction (FIII) effect on cholesterol metabolism: modulation of the low density lipoprotein receptor pathway

1. A heat stable protein fraction from calf thymus is able to determine a marked drop of total serum cholesterol and B apoproteins in rats fed a cholesterol enriched diet. 2. It is known that the catabolism of low density lipoprotein (LDL) cholesterol is mediated by the existence of high affinity surface receptor on membrane cells. 3. The purpose of the present paper is to verify if the heat stable thymus protein fraction is able to affect the LDL receptor pathway in vitro. 4. The results obtained show that the protein calf thymus is able to increase human and rat LDL catabolism.     

Protective effect of the oligomeric acylphloroglucinols from Myrtus communis on cholesterol and human low density lipoprotein oxidation

Myrtle (Myrtus communis L.), a culinary spice and flavouring agent for alcoholic beverages widespread in the Mediterranean area and especially in Sardinia, contains the structurally unique oligomeric non-prenylated acylphloroglucinols, semimyrtucommulone and myrtucommulone A, whose antioxidant activity was investigated during the oxidative modification of lipid molecules implicated in the onset of cardiovascular diseases. Both acylphloroglucinols showed powerful antioxidant properties during the thermal (140 degrees C), solvent-free degradation of cholesterol. Moreover, the pre-treatment with semimyrtucommulone and myrtucommulone A significantly preserved LDL from oxidative damage induced by Cu(2+) ions at 2h of oxidation, and showed remarkable protective effect on the reduction of polyunsaturated fatty acids and cholesterol, inhibiting the increase of their oxidative products (conjugated dienes fatty acids hydroperoxides, 7beta-hydroxycholesterol, and 7-ketocholesterol). Taking into account the widespread culinary use of myrtle leaves, the results of the present work qualify the natural compounds semimyrtucommulone and myrtucommulone A as interesting dietary antioxidants with potential antiatherogenicity.     

Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese

The aim of our study was to compare apolipoprotein B (apoB), non-high density lipoprotein cholesterol (nonHDL-C), low density lipoprotein cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD) in Chinese. Overall, 122 individuals developed CHD during a median 13.6 years of follow-up in 3,568 adult participants from a community-based cohort. The multivariate relative risk of CHD in the highest quintile compared with the lowest quintile was 2.74 [95% confidence interval (CI), 1.45-5.19] for apoB, 1.98 (95% CI, 1.00-3.92) for nonHDL-C, and 1.86 (95% CI, 1.00-3.49) for LDL-C (all tests for trend, P < 0.05). ApoB also had the highest receiver operator characteristic curve area (0.63; 95% CI, 0.58-0.68) in predicting CHD. When apoB and nonHDL-C were mutually adjusted, only apoB was predictive; the relative risk was 2.80 (95% CI, 1.31-5.96; P = 0.001) compared with 1.09 (95% CI, 0.49-2.40; P = 0.75) for nonHDL-C. Compared with the lowest risk, participants with the highest apoB and total cholesterol/HDL-C had a 3-fold increased risk of developing CHD (relative risk = 3.21; 95% CI, 1.45-7.14). These data provide strong evidence that apoB concentration was a better predictor of CHD than other lipid markers in Chinese.     

Type C Niemann-Pick disease. Lysosomal accumulation and defective intracellular mobilization of low density lipoprotein cholesterol

The intracellular accumulation of unesterified cholesterol was examined during 24 h of low density lipoprotein (LDL) uptake in normal and Niemann-Pick C fibroblasts by fluorescence microscopy with filipin staining and immunocytochemistry. Perinuclear fluorescence derived from filipin-sterol complexes was observed in both normal and mutant cells by 2 h. This perinuclear cholesterol staining reached its peak in normal cells at 6 h. Subsequent development of fluorescence during the remaining 18 h of LDL incubation was primarily limited to the plasma membrane region of normal cells. In contrast, mutant cells developed a much more intense perinuclear fluorescence throughout the entire 24 h of LDL uptake with little enhancement of cholesterol fluorescence staining in the plasma membranes. Direct mass measurements confirmed that internalized LDL cholesterol more readily replenishes the plasma membrane cholesterol of normal than of mutant fibroblasts. Perinuclear filipin-cholesterol fluorescence of both normal and mutant cells was colocalized with lysosomes by indirect immunocytochemical staining of lysosomal membrane protein. Abnormal sequestration of LDL cholesterol in mutant cells within a metabolically latent pool is supported by the finding that in vitro esterification of cellular cholesterol could be stimulated in mutant but not in normal cell homogenates by extensive disruption of the intracellular membranous structures of cells previously cultured with LDL. Deficient translocation of exogenously derived cholesterol from lysosomes to other intracellular membrane sites may be responsible for the delayed homeostatic responses associated with LDL uptake by mutant Niemann-Pick Type C fibroblasts.     

Effects of cardiovascular exercise early after stroke: systematic review and meta-analysis

ABSTRACT: BACKGROUND: Previous studies have shown the beneficial effects of aerobic exercise in chronic stroke. Most motor and functional recovery occurs in the first months after stroke. Improving cardiovascular capacity may have potential to precipitate recovery during early stroke rehabilitation. Currently, little is known about the effects of early cardiovascular exercise in stroke survivors. The aim of this systematic review was to evaluate the effectiveness of cardiovascular exercise early after stroke. METHODS: A systematic literature search was performed. For this review, randomised and nonrandomised prospective controlled cohort studies using a cardiovascular, cardiopulmonary or aerobic training intervention starting within 6 months post stroke were considered. The PEDro scale was used to detect risk of bias in individual studies. Inter-rater agreement was calculated (kappa). Meta-analysis was performed using a random-effects model. RESULTS: A total of 11 trials were identified for inclusion. Inter-rater agreement was considered to be "very good" (Kappa: 0.81, Standard Error: 0.06, CI95%: 0.70-0.92), and the methodological quality was "good" (7 studies) to "fair" (4 studies). Peak oxygen uptake data were available for 155 participants. Pooled analysis yielded homogenous effects favouring the intervention group (standardised mean difference (SMD) = 0.83, CI95% = 0.50-1.16, Z = 4.93, P < 0.01). Walking endurance assessed with the 6 Minute Walk Test comprised 278 participants. Pooled analysis revealed homogenous effects favouring the cardiovascular training intervention group (SMD = 0.69, CI95% = 0.45-0.94, Z = 5.58, P < 0.01). Gait speed, measured in 243 participants, did not show significant results (SMD = 0.51, CI95% = 0.25-1.26, Z = 1.31, P = 0.19) in favour of early cardiovascular exercise. CONCLUSION: This meta-analysis shows that stroke survivors may benefit from cardiovascular exercise during sub-acute stages to improve peak oxygen uptake and walking distance. Thus, cardiovascular exercise should be considered in sub-acute stroke rehabilitation. However, concepts to influence and evaluate aerobic capacity in severely affected individuals with subacute stroke, as well as in the very early period after stroke, are lacking. Further research is needed to develop appropriate methods for cardiovascular rehabilitation early after stroke and to evaluate long-term effects of cardiovascular exercise on aerobic capacity, physical functioning, and quality-of-life.     

Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins

Alzheimer''s disease (AD) is a heterogeneous neurodegenerative disorder and the most prevalent form of dementia worldwide. AD is characterized pathologically by amyloid-β plaques, neurofibrillary tangles and neuronal loss, and clinically by a progressive loss of cognitive abilities. At present, the fundamental molecular mechanisms underlying the disease are unclear and no treatment for AD is known. Epidemiological evidence continues to mount linking vascular diseases, such as hypertension and diabetes, and hypercholesterolaemia with an increased risk for developing AD. A growing amount of evidence suggests a mechanistic link between cholesterol metabolism in the brain and the formation of amyloid plaques in AD development. Cholesterol and statins clearly modulate β-amyloid precursor protein (βAPP) processing in cell culture and animal models. Statins not only reduce endogenous cholesterol synthesis but also exert other various pleiotrophic effects, such as the reduction in protein isoprenylation. Through these effects statins modulate a variety of cellular functions involving both cholesterol (and membrane rafts) and isoprenylation. Although clearly other factors, such as vascular inflammation, oxidative stress and genetic factors, are intimately linked with the progression of AD, this review focuses on the present research findings describing the effect of cholesterol, membrane rafts and isoprenylation in regulating βAPP processing and in particular γ-secretase complex assembly and function and AD progression, along with consideration for the potential role statins may play in modulating these events.     

Provision of cholesterol to lymphocytes by high density and low density lipoproteins. Requirement for low density lipoprotein receptors

The capacity of lipoprotein fractions to provide cholesterol necessary for human lymphocyte proliferation was examined. When endogenous synthesis of cholesterol was blocked, proliferation of mitogen-stimulated normal human lymphocytes was markedly inhibited unless an exogenous source of sterol was supplied. All lipoprotein fractions with the exception of high density lipoprotein subclass 3 were able to provide cholesterol for lymphocyte proliferation. Each of the lipoprotein subfractions capable of providing cholesterol was also able to regulate endogenous sterol synthesis in cultured human lymphocytes. Provision of cholesterol by lipoproteins required the interaction of apolipoprotein B or apolipoprotein E with specific receptors on normal lymphocytes. Apolipoprotein modification by acetylation or methylation, which markedly reduced the ability to regulate sterol biosynthesis, also diminished the capacity of lipoproteins to provide cholesterol. In addition, depletion of apolipoprotein B- and apolipoprotein E-containing particles from high density lipoprotein decreased its ability to suppress cholesterol synthesis and prevented it from providing cholesterol to proliferating lymphocytes. Monoclonal antibodies directed against the receptor-recognition sites on apolipoprotein B and apolipoprotein E were used to define the specific apolipoproteins required for the provision of cholesterol to lymphocytes by the various lipoprotein fractions. The antibody to apolipoprotein B inhibited cholesterol provision by both low density lipoprotein (LDL) and other lipoprotein fractions. The antibody to apolipoprotein E did not decrease provision of cholesterol by LDL but did inhibit the capacity of other fractions to provide cholesterol. In addition, a monoclonal antibody against the ligand binding site on the LDL receptor inhibited provision of cholesterol to normal lymphocytes by all lipoproteins. Finally, lymphocytes lacking LDL receptors were unable to obtain cholesterol from any lipoprotein fraction. These studies demonstrate that LDL receptor-mediated interaction with apolipoprotein B or apolipoprotein E is essential for the provision of cholesterol to normal human lymphocytes from all lipoprotein sources.