Cholesterol Journal Articles

Record 8341 to 8360

Lipoprotein pattern and plasma lecithin cholesterol acyl transferase activity in children with Alagille syndrome
Gottrand, F., V. Clavey, et al. (1995), Atherosclerosis 115(2): 233-41.
Abstract: Alagille syndrome is frequently associated with hyperlipidemia and xanthoma. The aim of the study was to assess the lipid profile (plasma lipoproteins, apolipoproteins (apo)) and lecithin cholesterol acyl transferase (LCAT) activity, with and without treatment with cholestyramine in Alagille syndrome. Five children (mean age = 6 +/- 4 years) with Alagille syndrome were studied at two different times while receiving no treatment, and while receiving cholestyramine. They were compared with 12 normal controls, who were not different from patients for age and sex. In Alagille syndrome, total serum cholesterol, triglycerides and phospholipids were elevated compared with the controls (P < 0.008). VLDL-cholesterol, LDL-cholesterol, HDL-triglycerides, LDL-triglycerides and VLDL-phospholipids were higher, whereas HDL-cholesterol was lower than controls (P < 0.03). Apo B, CIII, E and lipoprotein particles Lp AI were higher (P < 0.001), whereas Lp AI:AII was lower than controls (P < 0.03). Lipoprotein-X was present in the 5 children with Alagille syndrome and explained in part the elevation of plasma cholesterol, phospholipids, and apo CIII. LCAT activity was decreased (P < 0.01) and might cause some abnormalities of HDL with lower cholesterol, higher triglycerides, apo E and apo CIII contents than controls, and abnormalities of VLDL and LDL with higher cholesterol, triglycerides, phospholipids and apo B contents than controls. Some of the risk factors of atherosclerosis were found in Alagille syndrome, namely high levels of plasma cholesterol, LDL cholesterol, apo B, apo B/apo AI. Treatment with cholestyramine resulted in a few modifications to the lipid profile, while lipoprotein-X and the decrease of LCAT activity persisted.

Lipoprotein promotes caveolin-1 and Ras translocation to caveolae: role of cholesterol in endothelial signaling
Zhu, Y., H. L. Liao, et al. (2000), Arterioscler Thromb Vasc Biol 20(11): 2465-70.
Abstract: To explore the role of LDL in caveolin-Ras regulation in human endothelial cells (ECs), we incubated confluent human umbilical vein endothelial cells (HUVECs) with LDL. This resulted in a high steady-state caveolin-1 (Cav-1) expression at both the mRNA and protein levels. LDL exposure appeared not to regulate the abundance of Cav-1. Immunofluorescence staining showed that Cav-1 protein migrated from the cytoplasm to the cell membrane after LDL exposure. Cav-1 protein and cholesterol partitioned mainly into the caveola fractions, and LDL increased both Cav-1 and cholesterol in these fractions. Ras protein in caveola fractions was also increased by LDL. Increased Ras was detected in Cav-1 immunoprecipitated samples, and conversely, increased Cav-1 was found in Ras-immunoprecipitated samples. We also demonstrated LDL-increased Ras activity in HUVECs by measuring the GTP/GTP+GDP ratio of Ras with (32)Porthophosphate labeling in the cells. Finally, we determined the binding of (3)H-labeled free cholesterol and recombinant H-Ras to Cav-1 fusion proteins in vitro. Both cholesterol and Ras bound to full-length GST-Cav-1, scaffolding domain (61-101), and C-terminal (135-178) Cav-1 fusion peptides. Addition of cholesterol enhanced Ras binding to the full-length and scaffolding domain of Cav-1 but not to the C-terminal Cav-1. These findings strongly suggest a role for Cav-1 in cholesterol trafficking and cholesterol-mediated intracellular signaling, which may mediate EC activation by LDL.

Lipoprotein receptors and the control of plasma LDL cholesterol levels
Goldstein, J. L. and M. S. Brown (1992), Eur Heart J 13 Suppl B: 34-6.

Lipoprotein receptors, plasma cholesterol metabolism, and the regulation of cellular free cholesterol concentration
Fielding, C. J. (1992), Faseb J 6(13): 3162-8.
Abstract: Classical concepts of the regulation of plasma cholesterol levels involve roles for the "forward" delivery of low density lipoprotein (LDL) cholesterol from the liver to the peripheral tissues, mediated by the LDL receptor, and a "reverse" delivery of cholesterol in the form of high density lipoprotein (HDL) from the peripheral tissues to the liver. Candidate receptors for HDL in peripheral tissues and for chylomicrons in the liver have more recently been described, and a receptor of uncertain function recognizing chemically modified LDL has also been identified. The activities of all the well-characterized lipoprotein receptors, as well of major catalytic factors in plasma that regulate cholesterol esterification and cholesteryl ester transfer between lipoproteins, reflect the need to maintain plasma membrane free cholesterol level, and its direct and indirect effects within the membrane, within well-defined limits.

Lipoprotein response to a National Cholesterol Education Program step II diet with and without energy restriction
Flynn, M. M., J. M. Zmuda, et al. (1999), Metabolism 48(7): 822-6.
Abstract: This study examined the efficacy of a National Cholesterol Education Program (NCEP) step II diet (25% fat with < 7% saturated fat SFA) with and without moderate energy restriction. We tested the hypothesis that moderate energy restriction would improve the lipid profile resulting from an isoweight NCEP step II diet. Twenty hypercholesterolemic subjets (10 men and 10 postmenopausal women) consumed the following three controlled diets, each of 4 weeks' duration, as outpatients: (1) high-fat, high-saturated-fat diet to establish baseline lipids and isoweight energy requirements, (2) NCEP step II diet at isoweight energy, and (3) NCEP step II diet with an energy level 15% less than isoweight. The NCEP step II diet at isoweight energy reduced total cholesterol (TC) by 4% (P =.015), high-density lipoprotein cholesterol (HDL-c) by 13% (P <.0001), and HDL2-c by 40% (P <.0001). The TC:HDL-c ratio increased from 4.9 to 5.5 (P <.0001) and was increased in 19 of 20 subjects. Apolipoprotein B (apo B)-containing lipoproteins changed reciprocally: low-density lipoprotein cholesterol (LDL-c) decreased 4% (P =.008) and very-low-density lipoprotein cholesterol (VLDL-c) increased 29% (P <.0001). Apo B levels did not change. Compared with the NCEP isoweight diet the NCEP hypocaloric diet significantly reduced VLDL-c (-9%, P =.014) and apo B (-5%, P =.015). There was an additional reduction in TC (-4%, P =.073) and LDL-c (-4%, P =.126) with no change in HDL-c (P =.807). These data indicate that a NCEP step II diet with energy restriction produces a more desirable lipoprotein response than a NCEP step II isoweight diet. Neither NCEP step II diet improved the TC:HDL-c ratio.

Lipoprotein responses to fish, coconut and soybean oil diets with and without cholesterol in the Syrian hamster
Lin, M. H., S. C. Lu, et al. (1995), J Formos Med Assoc 94(12): 724-31.
Abstract: Thirty-six young male Syrian hamsters were fed with test diets containing coconut oil, soybean oil or fish oil with and without 0.5% cholesterol for 6 weeks. Without dietary cholesterol supplementation, animals on the fish oil diet had significantly lower plasma total triglyceride (TG) and total cholesterol than those on the coconut oil or soybean oil diet. The decrease of TG was seen mainly in the very low density lipoprotein (VLDL) fraction. The degree of decrease in cholesterol was similar in all of the lipoprotein fractions. With 0.5% dietary cholesterol supplementation, there was no significant difference in plasma TG level among the three dietary groups. However, the fish oil group had significantly higher plasma cholesterol than the coconut oil and soybean oil groups. The increase of cholesterol was mainly in the VLDL and low density lipoprotein (LDL) fractions. In contrast to the plasma cholesterol level, the hepatic cholesteryl ester content was significantly lower in the cholesterol-supplemented fish oil group than in the coconut oil and soybean oil counterparts. The cholesterol-supplemented fish oil group showed higher liver microsomal acyl-coenzyme A:cholesterol acyltransferase activity than the other two groups, while there was no significant difference in the excretion of fecal neutral and acidic sterols among the three dietary groups.

Lipoprotein(a) and cholesterol levels act synergistically and apolipoprotein A-I is protective for the incidence of primary acute myocardial infarction in middle-aged males. An incident case-control study from Sweden
Dahlen, G. H., L. Weinehall, et al. (1998), J Intern Med 244(5): 425-30.
Abstract: OBJECTIVE: To further establish the importance of total plasma apolipoprotein A-I and lipoprotein(a) in the prediction of primary acute myocardial infarction (AMI) in men. DESIGN: An incident case-control study. SETTING: The study was nested within the Vasterbotten Intervention Program (VIP) and the Northern Sweden MONICA cohorts. SUBJECTS: A total of 62 male AMI cases and 124 matched controls, randomly selected from the study cohorts. RESULTS: In multivariate logistic regression, significant odds ratios (OR) were found for Lp(a) above 200 mg L-1, apo A-I below the mean value (1136 mg L-1) and total cholesterol (TC) above 7.8 mmol L-1. TC interacted significantly with Lp(a); for Lp(a) above 200 mg L-1 and TC below 6.5 mmol L-1, OR = 5.6; for Lp(a) above 200 mg L-1 and TC above 6.5 mmol L-1, OR = 12.6. To evaluate the potential effect of reducing high levels of Lp(a) or TC on the incidence of AMI in males, the attributable risk percentage (ARP) was calculated when interaction between the two variables was present. ARP is 31% for Lp(a) and 21% for TC, implying that 31% of the cases are due to high Lp(a) and 21% of the cases are due to high TC levels. CONCLUSIONS: In the Swedish male population, total apo A-I in plasma is a protective factor and a plasma Lp(a) level above 200 mg L-1 is a risk factor for AMI in males. A TC level above 6.5 mmol L-1 increased the risk of AMI if the Lp(a) level was above 200 mg L-1, suggesting Lp(a) to be useful in identifying high risk individuals needed to be treated.

Lipoprotein(a)- and low-density lipoprotein-derived cholesterol in nephrotic syndrome: Impact on lipid-lowering therapy?
Kronenberg, F., A. Lingenhel, et al. (2004), Kidney Int 66(1): 348-54.
Abstract: BACKGROUND: Patients with nephrotic syndrome have the highest lipoprotein(a) Lp(a) concentrations known. Lp(a) is an low-density lipoprotein (LDL)-like particle consisting of 45% cholesterol. The usual methods to determine LDL cholesterol do not distinguish between cholesterol derived from LDL and Lp(a) and are thus the net result of cholesterol levels from both lipoproteins. High Lp(a) concentrations therefore significantly contribute to the measured or calculated LDL cholesterol levels. Since statins have no influence on Lp(a) levels, it can be expected that the LDL cholesterol-lowering effect of statins may be diminished in patients who have a pronounced elevation of Lp(a) levels accompanied by only moderate elevations of LDL cholesterol. METHODS: We investigated 207 patients with nondiabetic nephrotic syndrome in whom Lp(a) concentrations were strikingly elevated when compared to 274 controls (60.4 +/- 85.4 mg/dL vs. 20.0 +/- 32.8 mg/dL, P < 0.0001). RESULTS: According to National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Managing Dyslipidemias, almost 95% of these patients are candidates for a therapeutic intervention to lower LDL cholesterol. LDL cholesterol levels corrected for Lp(a)-derived cholesterol, however, were 27 mg/dL lower than uncorrected concentrations (compared to only 9 mg/dL in controls). If Lp(a)-corrected levels instead of total LDL cholesterol levels were used, 25.7% of patients with low-molecular-weight (LMW) apolipoprotein(a) apo(a) isoforms were classified no longer to be in need of LDL cholesterol-lowering therapeutic intervention compared to only 2.3% of patients with high-molecular-weight (HMW) apo(a) phenotypes (P < 0.00001). This ("pseudo") pharmacogenetic effect results in incorrect determination of LDL cholesterol. CONCLUSION: Our observation has an impact on the indication for, and assessment of efficacy of intervention. This potential artifact should be investigated in ongoing large trials in renal patients as well as in nonrenal African American subjects who have on average markedly higher Lp(a) levels. In nonrenal Caucasian subjects with much lower Lp(a) concentrations, this issue will be less relevant.

Lipoprotein(a) concentrations in non-selected hospitalised patients between 18 and 100 years of age: comparison with cholesterol fractions and triacylglycerols in patients with lipid status requests
Wood, W. G. and M. Schumacher (1995), Eur J Clin Chem Clin Biochem 33(12): 903-14.
Abstract: In a study designed to measure lipoprotein(a), cholesterol, cholesterol fractions and triacylglycerols in serum 4004 hospitalised individuals aged between 18 and 100 years were examined. Lipoprotein(a) was determined in 1313 patients (438 males, 875 females) aged 18-59 years and 489 patients (234 males, 255 females) aged 60-100 years. Cholesterol, cholesterol fractions and triacylglycerols were determined in a further 2037 patients (1084 males, 953 females) aged 18 to 100 years, for whom a lipid-status request had been made. Lipoprotein(a) concentrations in 619 females measured directly postpartum were not significantly different from aged-matched female in-patients (n = 104) and age-matched female hospital staff (n = 114). Lipoprotein(a) concentrations in women (n = 77) aged 30-74 undergoing chronic haemodialysis were significantly higher (p < 0.001) than in men (n = 95) of the corresponding age group. Median lipoprotein(a) serum concentrations showed a peak between 60-69 years in both men and women, i.e. at times of reported increased cardiovascular disease in both sexes. The lipoprotein(a) levels found in old age are comparable with those found in children and adolescents. The lipoprotein(a) patient group was assessed according to age and clinic. Eight groups of patients were analysed. The maternity patients were significantly younger (median age 26 a) than the other seven groups (p < 0.05 - < 0.01), the hospital employees (median age 31 a) attending the annual check-up being younger than the remaining six groups (p < 0.01). Lipoprotein(a) concentrations were marginally higher (p = 0.05) in the dialysis patients, when compared with those on internal medical wards. Of the 'traditional' lipid analytes, the ratio LDL-cholesterol:HDL-cholesterol was of interest, being significantly higher in males aged 70-79 years of age, when compared with males under 30 years of age. Triacylglycerols were higher in men aged between 30 and 59 years (p = 0.05 - < 0.01). The relationship between median analyte concentration and age was different for lipoprotein(a) than for the ratio LDL-cholesterol:HDL-cholesterol and triacylglycerols, thus further supporting the fact that lipoprotein(a) may be an independent risk factor for the development of atherosclerotic disease.

Lipoprotein(a), Friedewald formula, and NCEP guidelines. National Cholesterol Education Program
Scanu, A. M. (2001), Am J Cardiol 87(5): 608-9, A9.
Abstract: The Friedewald low-density lipoprotein cholesterol formula, which is commonly used in clinical chemistry laboratories, comprises both low-density lipoprotein and lipoprotein(a) cholesterol. This confounder must be recognized and appropriately corrected when dealing with subjects with high plasma lipoprotein(a) levels.

Lipoprotein(a)-cholesterol and coronary heart disease in the Framingham Heart Study
Seman, L. J., C. DeLuca, et al. (1999), Clin Chem 45(7): 1039-46.
Abstract: BACKGROUND: Increased plasma lipoprotein(a) Lp(a) concentrations have been reported to be an independent risk factor for coronary heart disease (CHD) in some prospective studies, but not in others. These inconsistencies may relate to a lack of standardization and the failure of some immunoassays to measure all apolipoprotein(a) isoforms equally. METHODS: We measured plasma Lp(a)-cholesterol Lp(a)-C in a Caucasian population of offspring and spouses of the Framingham Heart Study participants, using a lectin-based assay (LipoproTM). We compared the prevalence of increased Lp(a)-C to the presence of sinking pre-beta-lipoprotein (SPB). We also related Lp(a)-C concentrations to the prevalence of CHD risk in the entire population. RESULTS: The mean (+/- SD) Lp(a)-C concentration in the Framingham population (n = 3121) was 0.186 +/- 0.160 mmol/L, with no significant gender or age differences. The mean Lp(a)-C concentrations in the absence or presence of SPB were 0.158 +/- 0. 132 mmol/L and 0.453 +/- 0.220 mmol/L, respectively (P <0.0001). The mean Lp(a)-C concentration in men with CHD (n = 156) was 0.241 +/- 0. 204 mmol/L, which was significantly (P <0.001) higher, by 34%, than in controls. The odds ratio for CHD risk in men with Lp(a)-C >/=0. 259 mmol/L (>/=10 mg/dL), after adjusting for age, HDL-cholesterol, LDL-cholesterol, smoking, diabetes, blood pressure, and body mass index, was 2.293 (confidence interval, 1.55-3.94; P <0.0005). Lp(a)-C values correlated highly with a Lp(a)-mass immunoassay ApotekTM Lp(a); r = 0.832; P <0.0001; n = 1000. CONCLUSIONS: An increased Lp(a)-C value >/=0.259 mmol/L (>/=10 mg/dL) is an independent CHD risk factor in men with a relative risk of more than 2, but was inconclusive in women. Lp(a)-C measurements offer an alternative to Lp(a)-mass immunoassays and can be performed on automated analyzers.

Lipoprotein-cholesterol analysis during screening: accuracy and reliability
Bachorik, P. S., T. A. Cloey, et al. (1991), Ann Intern Med 114(9): 741-7.
Abstract: OBJECTIVE: To evaluate the accuracy and reliability of lipoprotein-cholesterol measurements obtained during screening. DESIGN: Cross-sectional study. PARTICIPANTS: From November 1989 to January 1990, 154 adults were screened. MEASUREMENTS: Split venous samples from fasting participants were analyzed for total cholesterol, triglyceride, and high-density-lipoprotein (HDL) cholesterol with screening and standardized laboratory methods. Low-density-lipoprotein (LDL)-cholesterol levels were calculated using the Friedewald equation. Split venous samples from nonfasting participants were analyzed for total cholesterol. Capillary blood samples were analyzed for total cholesterol with the screening method. MAIN RESULTS: Total cholesterol measurements in screening venous blood samples were 5.4% and 3.8% lower than the laboratory values in samples from fasting and nonfasting participants, respectively. Triglyceride and HDL-cholesterol values in venous samples obtained from fasting participants were, on average, 9.8% and 11.2% lower than the respective laboratory measurements. Screening HDL-cholesterol values varied, differing from the laboratory values by as much as 40% in 95% of participants. In fasting participants, total cholesterol in capillary samples averaged 5.5% higher than in venous samples; in nonfasting participants the capillary samples were 3.1% higher. Screening for either total cholesterol or LDL cholesterol identified 93% of the persons with LDL-cholesterol values of 3.36 mmol/L (130 mg/dL) or higher. CONCLUSIONS: Total cholesterol can be reliably measured in samples from fasting or nonfasting persons. The values in capillary blood samples were slightly higher than those in venous samples. Screening HDL-cholesterol values were too variable to establish the HDL-cholesterol level reliably. Participants with high LDL-cholesterol levels were identified as accurately by measuring total cholesterol only when compared with calculating the LDL-cholesterol level from total cholesterol, triglyceride, and HDL-cholesterol concentrations.

Lipoprotein-cholesterol levels in infertile women with luteal phase deficiency
Hansen, K. K., R. H. Knopp, et al. (1991), Fertil Steril 55(5): 916-21.
Abstract: OBJECTIVE: To determine if reductions in plasma progesterone (P) secretion seen in luteal phase deficiency (LPD) might be because of reduced availability of circulating low-density lipoprotein (LDL) or high-density lipoprotein (HDL), known substrates for corpus luteum P synthesis. DESIGN: We measured plasma lipoproteins in the luteal phase of the menstrual cycle in 39 infertile women. These women were divided into two groups on the basis of endometrial biopsies; the LPD group had biopsies that were greater than or equal to 3 days out-of-phase. SETTING: All participants were recruited from the Reproductive Endocrinology and Infertility Clinic at the University of Washington, an institutional tertiary care center. PATIENTS, PARTICIPANTS: Eighteen women had in-phase and 21 had out-of-phase LPD biopsies. MAIN OUTCOME MEASURE: Lipoprotein levels were obtained in a fasted state on the day of the luteal phase on which the biopsy was performed. RESULTS: No difference in covariates that affect lipoprotein levels such as obesity, age, and alcohol use were observed between the two groups. No significant differences between groups were found for triglycerides, total cholesterol, very low density lipoprotein, LDL, HDL, HDL2, and HDL3 concentrations. However, LPD was associated with a reduction in the extent to which: age and obesity are associated with higher triglycerides; obesity is associated with a lower HDL2; and alcohol is associated with a higher HDL3-cholesterol. CONCLUSIONS: Lipoproteins on average are not different in LPD, suggesting reasons other than a deficient plasma lipoprotein cholesterol source as the explanation for decreased P secretion. A lesser interaction between LDL or HDL and obesity, age, and alcohol in LPD could signify an influence of the altered hormonal milieu of LPD on the way lipoproteins interact with covariates and could lead to differences in lipoproteins between normal and LPD subjects at the extremes of the lipoprotein distribution.

Lipoprotein-cholesterol responses in healthy infants fed defined diets from ages 1 to 12 months: comparison of diets predominant in oleic acid versus linoleic acid, with parallel observations in infants fed a human milk-based diet
Mize, C. E., R. Uauy, et al. (1995), J Lipid Res 36(6): 1178-87.
Abstract: A prospective study in healthy infants predefining both diet fatty acid and cholesterol, from birth to age 1 year, compared response of cholesterol fractions in three groups: random assignment to 1) monounsaturated-(Hi-Mono) (n = 20), or 2) polyunsaturated-(Hi-Poly) (n = 22) fatty acid-enriched diets, or 3) non-randomized selection to breast feeding (Human Milk) (n = 25). In each group, designated weaning foods and supplements maintained fatty acid and cholesterol intake similar to that of each group's defined formulas, with long-term compliance confirmed by plasma phospholipid fatty acid concentrations. By 12 months, total cholesterol was significantly lower in the Hi-Poly group compared to either of the other groups (P < 0.05). Low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations were significantly lower by 12 months in the Hi-Poly group, compared to the Hi-Mono groups. However, at the earlier 4-month interval, total cholesterol and LDL-cholesterol in both Hi-Mono and Hi-Poly groups were not different from each other, although each was significantly lower than the parallel Human Milk-group (P < 0.05). The Hi-Mono group increased gradually in total and LDL-cholesterol such that, after 12 months' feedings, all lipid fractions of this Hi-Mono group were no different from those of the Human Milk group. In independent group comparisons, there were no significant differences in HDL-cholesterol concentrations after 4 and 9 months on these diets. Independent of diet, HDL-cholesterol showed a falling trend as an overall time-effect across all groups (P < 0.001). These data suggest that prolonged feeding of a diet enriched in polyunsaturated acids in early infancy has a significant cholesterol-lowering effect compared to monounsaturates. These differences in total, LDL-, and HDL-cholesterol plasma concentrations between polyunsaturates and monounsaturates were not significantly evident until feedings had continued for a year.

Lipoproteins activate acyl-coenzyme A:cholesterol acyltransferase in macrophages only after cellular cholesterol pools are expanded to a critical threshold level
Xu, X. X. and I. Tabas (1991), J Biol Chem 266(26): 17040-8.
Abstract: Activation of acyl-CoA:cholesterol actyltransferase (ACAT) in macrophages by lipoproteins is a key event in atheroma foam cell formation. To help elucidate the mechanisms whereby lipoproteins stimulate ACAT, the early cellular events of lipoprotein-induced ACAT stimulation were studied in mouse peritoneal macrophages. As a function of increasing lipoprotein-cholesterol influx to the cell during the first few hours of incubation, ACAT activity was markedly stimulated by beta-very low density lipoprotein (beta-VLDL) and acetyl-low density lipoprotein (acetyl-LDL) only after lipoprotein-cholesterol influx reached a threshold level of approximately 25% above the basal cell cholesterol content. In contrast, LDL stimulated ACAT only minimally at this level of lipoprotein-cholesterol influx. In further experiments, the source of ACAT cholesterol substrate during the initial stimulation of ACAT was shown to be a mixture of cellular (approximately 75%) and lipoprotein-cholesterol (approximately 25%) in proportions that approximated the proportions of originally cellular and lipoprotein-cholesterol in the cell. Thus, lipoprotein-cholesterol rapidly mixed with most or all of cellular cholesterol before ACAT esterification. Additional studies showed that LDL caused significant efflux of cellular cholesterol, thus providing at least a partial explanation for the relatively weak ACAT stimulatory potential of LDL. To support this idea, LDL that was modified to decrease its ability to induce net cellular cholesterol efflux stimulated ACAT 2-fold greater than control LDL when matched for lysosomal LDL-cholesterol influx. Moreover, when the effective efflux potentials of beta-VLDL and acetyl-LDL were increased, ACAT stimulation was markedly decreased despite unchanged lipoprotein-cholesterol influx. Thus, macrophage ACAT is stimulated not directly by the influx of newly hydrolyzed lipoprotein-cholesterol but rather by net expansion of cellular cholesterol pools to a particular threshold level. This scheme has potentially important implications regarding the cellular and molecular mechanisms of foam cell formation.

Lipoproteins and cellular cholesterol homeostasis
Johnson, W. J., M. C. Phillips, et al. (1997), Subcell Biochem 28: 235-76.
Abstract: Cholesterol homeostasis in peripheral cells involves a balance between the influx and efflux processes. The acquisition of cholesterol by such cells is mediated by a variety of receptor and non-receptor processes involving both normal and modified lipoproteins. The offsetting efflux process is mediated by HDL and especially particles containing only apo A-I. An efficient reverse cholesterol transport by HDL of cholesterol from peripheral cells to the liver protects against the development of atherosclerosis. In cells that do not contain excess cholesterol, the cholesterol is distributed as unesterified cholesterol molecules between the plasma membrane and the membranes of the intracellular organelles. In cholesterol-loaded cells such as macrophage foam cells, the membranes became enriched in unesterified cholesterol and, in addition, cytoplasmic CE droplets and lysosomal cholesterol crystals can form. The ways in which cholesterol molecules move between intracellular sites and the plasma membrane to become available for efflux to extracellular acceptor particles are becoming known. Cholesterol molecules in the plasma membrane can desorb and diffuse through the aqueous phase and be sequestered by HDL particles. The cell cholesterol available for efflux can exist in different kinetic pools, and these pools, such as those in various domains in the plasma membrane, require further definition. The cholesterol molecules present in intracellular pools also efflux with different kinetics and by different pathways. Thus, newly synthesized cholesterol is actively transported by a vesicle system from the ER to the plasma membrane, whereas lysosomal cholesterol seems to be transported to the plasma membrane by a protein-mediated, diffusional process. Clearance of cytoplasmic CE is dependent upon the rate of turnover of the CE cycle and the magnitude of the cholesterol gradient between the plasma membrane and the extracellular acceptor particle. It can be expected that the interdependence of the pathways and the molecular mechanisms underlying the intracellular trafficking of cholesterol will be elucidated in the near future.

Lipoproteins are protective beyond high-density lipoprotein cholesterol and heart disease
Harris, H. W. (2005), Crit Care Med 33(8): 1859-60.

Lipoproteins containing apolipoprotein A-I and reverse transport of cholesterol
Fruchart, J. C. (1994), Ann Pharm Fr 52(3): 117-23.
Abstract: The antiatherogenic HDLs are heterogeneous in terms both of hydrated density and of lipoprotein composition. The LpA-I and LpA-I: A-II particles seem to be different from a metabolic point of view, and LpA-I and LpA-IV are apparently the only ones involved in the antiatherogenic action of HDLs. Alcohol consumption causes an increase in LpA-I: A-II, but not in LpA-I. Specific HDL binding sites have been demonstrated in various tissues, including steroidogenic tissues, liver cells and peripheral cells. Apolipoproteins A-I, A-IV and A-II are possible ligands. After binding to the uptake site, HDLs allow cholesterol supply to the cells, on one hand, and the removal of cholesterol for "reverse cholesterol transport" from peripheral tissues to the liver on the other hand. In addition, the interaction of the various HDL subfractions can cause different metabolic effects: cholesterol efflux from the adipocytes of cholesterol-laden mice is influenced by the uptake of LpA-I and LpA-IV on receptors, while apolipoproteins A-II are antagonists for this effect.

Lipoproteins containing apolipoprotein A-IV but not apolipoprotein A-I take up and esterify cell-derived cholesterol in plasma
von Eckardstein, A., Y. Huang, et al. (1995), Arterioscler Thromb Vasc Biol 15(10): 1755-63.
Abstract: Two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis (2D-PAGGE) identifies distinct apoA-I-or apoE-containing subclasses of high-density lipoproteins (HDLs), each of which plays a different role in reverse cholesterol transport. In this study we used 2D-PAGGE to investigate the role of apoA-IV-containing lipoproteins in reverse cholesterol transport in native plasma. Incubation of 2D electrophoretograms with anti-apoA-IV antibodies identified up to three subclasses of particles. The smaller particle subclasses, LpA-IV-1 and LpA-IV-2, were found in every plasma sample. The largest particle subclass, LpA-IV-3, was observed in fewer than 10% of the plasmas analyzed. 2D-PAGGE of apoA-I-deficient plasma and apoA-I-depleted plasma and anti-apoA-I immunosubtracting 2D-PAGGE of normal plasma revealed that LpA-IV-1 and LpA-IV-2 do not contain apoA-I. The importance of LpA-IV-1 and LpA-IV-2 for uptake and esterification of cell-derived cholesterol was investigated using pulse-chase incubations of plasma with 3Hcholesterol-labeled fibroblasts followed by anti-apoA-I immunosubtracting 2D-PAGGE. During 1-minute pulse incubation with cells, 3Hcholesterol was taken up by gamma-LpE > LpA-IV-1 > pre-beta 1-LpA-I > LpA-IV-2 (">" denotes "more than"). During subsequent chase incubation without cells, proportionately less radioactivity disappeared from LpA-IV-1 and LpA-IV-2 than from pre-beta 1-LpA-I and gamma-LpE. During 5-minute pulse incubations, radioactive cholesteryl esters were formed in pre-beta 3-LpA-I > alpha-LpA-I > LpA-IV-1 > LpA-IV-2. The fractional estertification rate was highest in pre-beta 2-LpA-I and lowest in alpha-LpA-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoproteins containing apolipoprotein A-IV: composition and relation to cholesterol esterification
Duverger, N., N. Ghalim, et al. (1994), Biochim Biophys Acta 1211(1): 23-8.
Abstract: In order to investigate the relationship of lipid and apolipoprotein composition to cholesterol esterification in lipoproteins containing apolipoprotein (apo) A-IV, apo A-containing lipoprotein particles were isolated from fresh human plasma using a system of sequential immunoaffinity chromatography. Plasma was first depleted of apo B- and apo E-containing lipoproteins. Four major subpopulations of apo A-containing lipoprotein particles were separated: Lp A-I, Lp A-I: A-II, Lp A-IV and Lp A-I: A-IV: A-II. Lp A-IV and Lp A-I: A-IV: A-II contained less total lipid, less cholesterol and more triacylglycerol than Lp A-I and Lp A-I: A-II. Lp A-IV and Lp A-I: A-IV: A-II contained more sphingomyelin and less phosphatidylcholine than Lp A-I and Lp A-I: A-II and were richer in (16:0 + 18:0) saturated fatty acids. Among these isolated lipoprotein particles, Lp A-IV contained the highest lecithin: cholesterol acyltransferase (LCAT) activity per micrograms of protein. Cholesterol esterification rates were 2.6 +/- 0.5, 5.3 +/- 0.4 and 0.8 +/- 0.2 mumol of cholesterol per hour per mg of lipoproteins for Lp A-IV, Lp A-I and Lp A-I: A-II, respectively. The apolipoprotein and lipid composition and LCAT activity of Lp A-IV suggest that this lipoprotein may be a source of cholesterol esterification in plasma.

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