| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Immunoaffinity beads for selective removal of cholesterol from human plasma Yavuz, H. and A. Denizli (2003), J Biomater Sci Polym Ed 14(5): 395-409. Abstract: Anti-low density lipoprotein antibody (anti-LDL antibody) attached poly(2-hydroxyethyl methacrylate-methacryloylamidophenylalanine) (poly(HEMA-MAPA)) beads were prepared for selective removal of cholesterol from hypercholesterolemic human plasma. Poly(HEMA-MAPA) beads were produced by a modified suspension polymerization and then characterized by swelling tests and SEM. Blood-compatibility tests were also investigated. The water swelling ratio of the poly(HEMA-MAPA) beads increased significantly (68%) compared with pHEMA (55%). All the clotting times increased when compared with poly(HEMA) beads. Loss of platelets and leukocytes was very low. The maximum anti-LDL antibody attachment was achieved at pH 7.0. Attachment of anti-LDL antibody was 29.6 mg/g. There was a very low non-specific cholesterol binding onto the poly(HEMA-MAPA) beads, about 0.74 mg/g. Anti-LDL antibody attached beads adsorbed in the range of 13.3-16.0 mg cholesterol/g from hypercholesterolemic human plasma. Up to 92% of the adsorbed LDL was desorbed. The binding-elution cycle was repeated 10 times using the same beads. There was no significant loss of binding capacity. |
| Immunochromatographic membrane strip assay system for a single-class plasma lipoprotein cholesterol, exemplified by high-density lipoprotein cholesterol measurement Paek, S. H., M. R. Jang, et al. (1999), Biotechnol Bioeng 62(2): 145-54. Abstract: In assessing risk factors of coronary heart disease, a membrane immunochromatographic system that minimizes requirements of instrument and reagent handling was investigated by utilizing high-density lipoprotein (HDL) cholesterol (HDL-C) as model analyte. The system is composed of four functional membrane strip pads connected in sequence as follows (from the bottom): immunoseparation based on the biotin-streptavidin reaction; catalytic conversion of cholesterol to hydrogen peroxide; production of a colorimetric signal; and induction of a continuous wicking of medium. For immunochromatography, a monoclonal antibody, specific to apolipoprotein B100 that is present on the surfaces of low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), with a high binding constant (5 x 10(10) L/mol), was raised and chemically conjugated to streptavidin. The conjugate was first reacted with lipoprotein particles, and this mixture was absorbed by the capillary action into the biotin pad of the system. After being transferred by medium, immunocapture of LDL and VLDL particles onto the biotin pad took place, and in situ generation of a colorimetric signal in proportion to HDL-C occurred consecutively. The capture was selective as well as effective (minimum 88% of LDL and VLDL in clinical concentration ranges), and the detection limit of the HDL-C was far lower than 20 mg per 100 mL. The same concept may also be applicable to LDL cholesterol measurement provided suitable antibodies specific to HDL and VLDL are available. |
| Immunoelectron microscopic localization of cholesterol using biotinylated and non-cytolytic perfringolysin O Mobius, W., Y. Ohno-Iwashita, et al. (2002), J Histochem Cytochem 50(1): 43-55. Abstract: We used a proteolytically modified and biotinylated derivative of the cholesterol-binding Theta-toxin (perfringolysin O) to localize cholesterol-rich membranes in cryosections of cultured human lymphoblastoid cells (RN) by electron microscopy. We developed a fixation and immunolabeling procedure to improve the preservation of membranes and minimize the extraction and dislocalization of cholesterol on thin sections. We also labeled the surface of living cells and applied high-pressure freezing and subsequent fixation of cryosections during thawing. Cholesterol labeling was found at the plasma membrane, with strongest labeling on filopodium-like processes. Strong labeling was also associated with internal vesicles of multivesicular bodies (MVBs) and similar vesicles at the cell surface after secretion (exosomes). Tubulovesicular elements in close vicinity of endosomes and the Golgi complex were often positive as well, but the surrounding membrane of MVBs and the Golgi cisternae appeared mostly negative. Treatment of cells with methyl-beta-cyclodextrin completely abolished the labeling for cholesterol. Our results show that the Theta-toxin derivative, when used in combination with improved fixation and high-pressure freezing, represents a useful tool for the localization of membrane cholesterol in ultrathin cryosections. |
| Immunoglobulins and alpha 1-acid glycoprotein do not contribute to the cholesterol crystallization-promoting effect of concanavalin A-binding biliary protein de Bruijn, M. A., K. S. Mok, et al. (1994), Hepatology 20(3): 626-32. Abstract: Human bile contains cholesterol crystallization-stimulating proteins that can be isolated by concanavalin A-Sepharose chromatography. In the past few years an increasing number of different pronucleating proteins have been identified in the concanavalin A-binding fraction. In this study we attempted to estimate the relative contribution of a number of these proteins to total concanavalin A-binding pronucleating activity. For this purpose, concanavalin A-binding glycoproteins were isolated from gallbladder bile samples from 12 patients with gallstones. The role of IgA, IgG and IgM and alpha 1-acid glycoprotein was investigated by means of immunoextraction. No decrease in crystallization-promoting activity was observed after precipitation of more than 98% of the different immunoglobulins. In addition, removal of more than 95% of alpha 1-acid glycoprotein from different concanavalin A-binding fractions had no significant effect on cholesterol crystallization-promoting activity. The influence of fibronectin was estimated by addition of physiological concentrations to a model bile system. At these concentrations fibronectin did not promote crystallization. From these data we conclude that immunoglobulins, alpha 1-acid glycoprotein and probably also fibronectin do not significantly contribute to total concanavalin A-binding activity. |
| Immunoglobulins as nucleating proteins in the gallbladder bile of patients with cholesterol gallstones Harvey, P. R., G. A. Upadhya, et al. (1991), J Biol Chem 266(21): 13996-4003. Abstract: The gallbladder bile of patients with cholesterol gallstones contains pronucleating proteins which accelerate precipitation of cholesterol crystals from bile. In this study we have improved the purification procedure developed earlier for these nucleating proteins and have now identified the nature of these proteins. Gallbladder bile from patients with cholesterol gallstones was applied to concanavalin A affinity columns. The ConA-binding glycoprotein fractions containing the nucleating proteins were then separated by FPLC (fast protein liquid chromatography) using a Superose 12 gel filtration column. Nucleating activity was detected in the high molecular weight (FPLC-1) as well as in the low molecular weight fractions (FPLC-3). Investigation of the high molecular weight fraction by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroelution and amino acid sequencing suggested that these proteins were immunoglobulins. Immunostaining of Western blots with specific monoclonal antibodies identified the presence of immunoglobulin (Ig) M and IgA in the FPLC-1 fraction. These immunoglobulins were further purified by affinity chromatography employing an antibody exchanger (ABx) column which specifically binds immunoglobulins. There was no reduction in the cholesterol nucleating activity in the Abx-bound fraction compared to FPLC-1. Additional studies showed that the FPLC-1 fraction was significantly more potent than the ConA glycoproteins from either rapid and slow nucleating biles. Also the number of crystals formed was significantly greater in the FPLC-1 fraction isolated from cholesterol gallstone biles than from the FPLC-1 fraction from control patient biles. Commercially obtained IgM and IgA had no effect on nucleation, but IgM isolated from the serum of patients with Waldenstrom's macroglobulinemia did accelerate the nucleation of cholesterol. We conclude that the IgM and possibly IgA are pronucleating proteins and may be important in the pathogenesis of cholesterol gallstones in man. |
| Immunohistochemical detection of macrophage-derived foam cells and macrophage colony-stimulating factor in pulmonary atherogenesis of cholesterol-fed rabbits Ruan, Y., K. Takahashi, et al. (1995), Pathol Int 45(3): 185-95. Abstract: In order to investigate the role of monocyte/macrophages and their relationship to the expression of macrophage colony-stimulating factor (MCSF) in pulmonary atherosclerosis, lungs were excised from rabbits that had been fed for 60 and 90 days on a diet containing 0.5% cholesterol. In the lungs, fatty streaks and elevated foam cell lesions predominated in the large or medium-sized elastic pulmonary arteries, while massive accumulation of foam cells in the intima of muscular arteries produced marked luminal narrowing and nearly complete occlusion. In these lesions, most of the foam cells were reactive with RbM2, a monoclonal antibody (mAb) against rabbit macrophages, while smooth muscle cell-derived foam cells were detected by mAb against smooth muscle actin in the deeper area of elevated foam cell lesions of elastic arteries. Ultrastructural observation confirmed the presence of monocytes in the intima, their differentiation into macrophages, and their transformation into foam cells in the atherosclerotic lesions. Immunohistochemical expression of MCSF was demonstrated in the endothelial cells, smooth muscle cells and foam cells. A minor macrophage-derived foam cell population was demonstrated to possess a proliferative capacity. These data suggest that MCSF is involved in the differentiation of monocytes into macrophages, their transformation into foam cells, and their proliferation during pulmonary atherogenesis. |
| Immunohistochemical detection of macrophages and T lymphocytes in atherosclerotic lesions of cholesterol-fed rabbits Hansson, G. K., P. S. Seifert, et al. (1991), Arterioscler Thromb 11(3): 745-50. Abstract: Human atherosclerotic plaques contain significant numbers of T lymphocytes and monocyte-derived macrophages. Cytokines released from activated T lymphocytes induce aberrant expression of major histocompatibility complex class II (Ia) antigens by vascular smooth muscle cells and may also regulate cell proliferation and metabolism in the vessel wall. We have analyzed the arteries of cholesterol-fed rabbits to study the sequence of lymphocyte and monocyte entry into the forming atherosclerotic lesion. Rabbits were fed 0.3% cholesterol for 1-10 weeks, and monoclonal antibodies to rabbit leukocyte differentiation antigens and Ia antigen were applied to sections of the aorta. Monocytes were already observed 1 week after initiation of cholesterol feeding, and they accumulated in the intima, where they formed the bulk of the foam cell-rich lesion. T lymphocytes also adhered to the aortic surface from 1 week onward, and also accumulated in the lesion, although in lower proportions than did monocytes. In 10-week lesions, approximately 6% of cells expressed the T-lymphocyte marker L11/135. Ia antigen expression was frequent throughout the lesion in all phases of its development, and most of the Ia-expressing cells could be identified as monocyte-derived macrophages. These data indicate that the cholesterol-fed rabbit is a useful model for studying the role of monocytes and T lymphocytes in atherosclerosis. |
| Immunolocalization of acyl-coenzyme A:cholesterol O-acyltransferase in macrophages Khelef, N., X. Buton, et al. (1998), J Biol Chem 273(18): 11218-24. Abstract: Macrophages in atherosclerotic lesions accumulate large amounts of cholesteryl-fatty acyl esters ("foam cell" formation) through the intracellular esterification of cholesterol by acyl-coenzyme A:cholesterol O-acyltransferase (ACAT). In this study, we sought to determine the subcellular localization of ACAT in macrophages. Using mouse peritoneal macrophages and immunofluorescence microscopy, we found that a major portion of ACAT was in a dense reticular cytoplasmic network and in the nuclear membrane that colocalized with the luminal endoplasmic reticulum marker protein-disulfide isomerase (PDI) and that was in a similar distribution as the membrane-bound endoplasmic reticulum marker ribophorin. Remarkably, another portion of the macrophage ACAT pattern did not overlap with PDI or ribophorin, but was found in as yet unidentified cytoplasmic structures that were juxtaposed to the nucleus. Compartments containing labeled beta-very low density lipoprotein, an atherogenic lipoprotein, did not overlap with the ACAT label, but rather were embedded in the dense reticular network of ACAT. Furthermore, cell-surface biotinylation experiments revealed that freshly harvested, non-attached macrophages, but not those attached to tissue culture dishes, contained approximately 10-15% of ACAT on the cell surface. In summary, ACAT was found in several sites in macrophages: a cytoplasmic reticular/nuclear membrane site that overlaps with PDI and ribophorin and has the characteristics of the endoplasmic reticulum, a perinuclear cytoplasmic site that does not overlap with PDI or ribophorin and may be another cytoplasmic structure or possibly a unique subcompartment of the endoplasmic reticulum, and a cell-surface site in non-attached macrophages. Understanding possible physiological differences of ACAT in these locations may reveal an important component of ACAT regulation and macrophage foam cell formation. |
| Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment Apour, C. S., S. J. Bell, et al. (1994), JPEN J Parenter Enteral Nutr 18(4): 381-3. |
| Immunomodulating action of essentiale during prolonged intake of dietary cholesterol Bart, E. V. and L. G. Prokopenko (1995), Patol Fiziol Eksp Ter(4): 15-8. Abstract: Light red blood cells from the rabbits on cholesterol diet were found to have immunosuppressing properties. The extracorporeal treatment of red blood cells with essentiale, heavy erythrocytes acquired immunostimulating properties. Light red blood cells lost their immunosuppressive capacity. The administration of linetol caused no changes in the immunomodulating properties of red blood cells from the rabbits taking cholesterol for a long time. |
| Immunoseparation method for measuring low-density lipoprotein cholesterol directly from serum evaluated McNamara, J. R., T. G. Cole, et al. (1995), Clin Chem 41(2): 232-40. Abstract: Low-density lipoprotein (LDL) cholesterol can not be calculated from other lipid measurements when samples are obtained from nonfasting individuals or when triglycerides are > or = 4.0 g/L. We have evaluated a direct LDL cholesterol assay for analyzing 115 fresh serum samples obtained from fasting and nonfasting dyslipidemic patients with triglycerides < or = 35.85 g/L, who were receiving diet and (or) drug treatments. Results were highly correlated with those by ultracentrifugation (r = 0.97), with a mean/median bias of -2.9%/0.7% (-0.001/0.010 g/L) and an absolute bias of 9.5%/6.4% (0.119/0.090 g/L). The assay correctly classified LDL cholesterol concentrations < 1.30 g/L 81% of the time, 1.30-1.60 g/L 76% of the time, and > or = 1.60 g/L 94% of the time. Precision studies provided within- and between-run CVs in the range of 1.2-3.8% and 2.0-5.1%, respectively. Our data indicate that this assay is an accurate method for measuring LDLC directly from fresh serum obtained from fasting or nonfasting subjects with a wide range of triglyceride values. |
| Impact of a cholesterol enriched diet on maternal and fetal plasma lipids and fetal deposition in pregnant rabbits Montoudis, A., L. Simoneau, et al. (1999), Life Sci 64(26): 2439-50. Abstract: Pregnancy is associated with a hypercholesterolemic and a hyperlipidemic state. The totality of the essential fatty acids and 50% of the lipids needed by the fetus are transferred by the placenta from the maternal circulation. The hypothesis of this study is that an augmentation of the maternal plasmatic cholesterol is modifying the fetal lipids accumulation and development during rabbit pregnancy. To demonstrate the impact of a cholesterol enriched diet on plasma lipids during rabbit's pregnancy and on their fetus, we have established two groups: control and hypercholesterolemic rabbits (fed with a 0.2% cholesterol diet). Blood samples were collected before mating and at each trimester of pregnancy for analysis of lipid fractions and their lipoproteins. Plasma analysis shows that starting the 10th day of pregnancy the concentration of total-cholesterol and lipoproteins decreases for both groups. We have demonstrated that for the hypercholesterolemic group, concentrations of total-cholesterol (631%) and lipoproteins are significantly higher at the end of pregnancy than those for the control group. For both groups, after 20 days of pregnancy, triglycerides metabolism was biphasic showing a significant increase followed by a diminution in their concentration. In both groups, free fatty acids increases significantly at the end of the pregnancy (537.5% for the control group and 462.5% for the hypercholesterolemic group). Furthermore, the offsprings of hypercholesterolemic dams manifest a lower birth weight (15.5%) than those of control group. Our results demonstrate that a cholesterol enriched diet modifies greatly the fetal development and lipid metabolism during rabbit's pregnancy. These modifications could be useful for the understanding of the interaction between diet and fetal development in rabbit and probably during human pregnancy. |
| Impact of a combination of a calcium antagonist and a beta-blocker on cell- and copper-mediated oxidation of LDL and on the accumulation and efflux of cholesterol in human macrophages and murine J774 cells Lesnik, P., C. Dachet, et al. (1997), Arterioscler Thromb Vasc Biol 17(5): 979-88. Abstract: Calcium antagonists and beta-blockers may retard or inhibit atherogenesis. In the absence of data pertaining to the potential cardioprotective action of an association of such agents, we have investigated the impact of nifedipine and atenolol, alone or in combination, on the capacity of monocyte-macrophages (ex vivo) and copper ions (in vitro) to oxidize LDL and on intracellular metabolism and efflux of free and esterified forms of cholesterol in human macrophages and foam cells. At concentrations up to 100 micromol/L, atenolol had no effect on the oxidative resistance of LDL; on the contrary, nifedipine displayed a significant dose-dependent capacity to protect LDL during copper-mediated oxidation (100 micromol/L; P<.001). Using a DPPH radical generating system, nifedipine was shown to exert free radical-trapping activity (molar ratio of scavenging activity, nifedipine:alpha-tocopherol, 1:114). The addition of atenolol to nifedipine was without effect on the antioxidant activity of the calcium antagonist. In experiments in which oxidative modification was mediated by monocyte-macrophages, nifedipine but not atenolol conserved its antioxidant capacity. Furthermore, we demonstrated that association of atenolol with nifedipine did not modify the antioxidant properties of nifedipine itself. Using a human monocyte-derived macrophage culture system, nifedipine, atenolol, or a combination of the two drugs was ineffective in inhibiting foam cell formation induced by acetylated LDL or oxidized LDL. However, atenolol (100 micromol/L) increased cellular accumulation of cholesteryl ester (+17%; P<.05), whereas nifedipine (100 micromol/L) decreased total cholesterol (-37.4%; P<.05) accumulation induced by acetylated LDL in the mouse macrophage cell line J774. A combination of the two drugs neutralized these antagonistic effects. None of these results were reproduced during the oxidized LDL-induced transformation of murine J774 cells into foam cells. Furthermore, cholesterol efflux from preloaded human macrophages was equally unaffected by the addition of the drugs alone or in combination. It therefore seems unlikely that the beneficial effect of atenolol on coronary heart disease is mediated by changes in either LDL oxidizability or cholesterol metabolism in human macrophages and foam cells. Our findings with nifedipine suggest, however, that this calcium antagonist may potentially exert antiatherosclerotic properties via a reduction of the oxidative modification of LDL, thereby affecting a reduction in foam cell formation and in the pathophysiological cellular activities of oxidized lipids, rather than by inducing a direct reduction in cholesterol accumulation in human foam cells of macrophage origin. |
| Impact of a public cholesterol screening program Fischer, P. M., K. H. Guinan, et al. (1990), Arch Intern Med 150(12): 2567-72. Abstract: The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L 9 mg/dL) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease. |
| Impact of an enriched-cholesterol diet on enzymatic cholesterol metabolism during rabbit gestation Montoudis, A., S. Boileau, et al. (2003), Life Sci 73(11): 1463-77. Abstract: An appropriate cholesterol homeostasis is vital for the maintenance and the optimal fetal development. The cholesterol is essential for the synthesis of progesterone and 17beta-estradiol, hormones that actively participate to sustain gestation. However, the administration of 0.2% enriched cholesterol diet (ECD) during rabbit gestation significantly increased the cholesterol blood profile (total-cholesterol, LDL, HDL, esterified-cholesterol and free-cholesterol) of dams and offspring, and induced a reduction of the offspring weight of 15% as compared to the control group. Enzymes involved in cholesterol metabolism (ACAT, HMG-CoA-reductase and cholesterol-7alpha-hydroxylase) are greatly influenced by cholesterol profile. We hypothesized that the administration of an ECD during rabbit gestation modifies the activity of those enzymes. Female rabbits (pregnant or not) were fed with a standard diet or an ECD. At term, livers (dams and offspring) and placentas were collected and ACAT, HMG-CoA-reductase and cholesterol-7alpha-hydroxylase activities were assayed. Our results demonstrate that gestation induced a reduction of ACAT activity (48.9%) in dam's liver and, an augmentation of HMG-CoA-reductase activity (142.4%) whereas it has no effect on cholesterol-7alpha-hydroxylase activity. The administration of the ECD has no additive effect on ACAT, but significantly reduced the HMG-CoA-reductase activity and cholesterol-7alpha-hydroxylase activity as compared with the pregnant control group. In placentas the ECD supplementation has an influence for HMG-CoA-reductase activity, where a 43% increased in observed. Any ACAT activity was detected in placenta and the ECD has no influence on the cholesterol-7alpha-hydroxylase activity. Whereas their offspring's liver present a reduction of ACAT and HMG-CoA-reductase activity. Gestation associated with ECD reduces significantly the HMG-CoA-reductase activity, decreasing the cholesterol synthesis, but placenta seems to compensate this effect by increasing its HMG-CoA-reductase activity. |
| Impact of apo E phenotype on the regulation of cholesterol metabolism Miettinen, T. A. (1991), Ann Med 23(2): 181-6. Abstract: Cholesterol absorption was positively related to the apo E subscript in middle aged men on their normal home diet. The apo E subscript (e.g. E2/2 = 1, E2/3 = 2, E2/4 = 3.) was negatively associated with cholesterol synthesis and fractional removal of LDL apo B and positively with the total and LDL cholesterol and LDL apo B concentrations. Cholesterol elimination, especially as bile acids, was most effective in subjects with epsilon 2 allele. A slight reduction of biliary deoxycholic acid content in the men with the epsilon 4 allele and a negative correlation between deoxycholic acid and cholesterol absorption suggested that intestinal bacterial function may contribute to the positive association of cholesterol absorption to the apo E phenotype. Reduction of fat and cholesterol consumption lowered while an increase of dietary cholesterol enhanced the LDL cholesterol concentration proportionately to the apo E subscript when cholesterol absorption efficiency was reduced in proportion to fat intake. Low absorption, effective elimination and high synthesis of cholesterol associated with low synthesis and effective removal of LDL apo B seem to be factors keeping serum cholesterol low during different diets. The findings also suggest that the apo E phenotypes regulate cholesterol metabolism during basal conditions and serum cholesterol responses to dietary modifications. |
| Impact of ApoE4 allele on total cholesterol levels of children in northern Spain Bercedo-Sanz, A., D. Gonzalez-Lamuno, et al. (1999), Clin Genet 55(1): 69-70. |
| Impact of apolipoprotein E polymorphism in determining interindividual variation in total cholesterol and low density lipoprotein cholesterol in Hispanics and non-Hispanic whites Kamboh, M. I., C. E. Aston, et al. (1993), Atherosclerosis 98(2): 201-11. Abstract: The extent of apolipoprotein E (apo E) polymorphism and its effect on eight quantitative risk factors for coronary heart disease (total cholesterol; low density lipoprotein (LDL) cholesterol; total high density lipoprotein and its subfractions, HDL2 and HDL3; triglycerides; fasting glucose and fasting insulin) has been determined in 238 randomly selected Hispanics (120 males and 118 females) and 201 non-Hispanic whites (NHWs) (105 males and 96 females) from the San Luis Valley, Colorado. The frequencies for the E * 2, E * 3 and E * 4 alleles were 0.048, 0.853 and 0.099, respectively, in Hispanics and 0.080, 0.783 and 0.137, respectively, in NHWs. Relatively low frequency of the E * 2 and E * 4 alleles in Hispanics compared with NHWs is consistent with the genetic and anthropologic data that Hispanics have substantial Amerindian admixture. The impact of apo E polymorphism on each quantitative trait was estimated after adjusting for concomitant variables including age, cigarette smoking and body mass index in both genders and pre- or post-menopause status in females. The distribution of eight quantitative traits was analyzed among three common apo E phenotypes, 3-2, 3-3 and 4-3. In Hispanics, significant variability among apo E phenotypes was observed for total cholesterol (P = 0.001) in females only and the apo E polymorphism accounts for 12.4% variation in total cholesterol and 15.2% variation in LDL-cholesterol. In NHWs, significant mean differences among apo E phenotypes were observed for total cholesterol in both males (P = 0.007) and females (P = 0.0004). In NHW males and females, the apo E polymorphism explained 9.2% and 12.4%, respectively, of the variation in total cholesterol, and 15.1% and 6.6%, respectively, of the variation in LDL-cholesterol. In NHWs, borderline significance levels were also noted for phenotype specific differences in HDL2-cholesterol in males (P = 0.04) and females (P = 0.05), for total HDL cholesterol in females (P = 0.02) and HDL3-cholesterol in females (P = 0.06). While the estimated effects of the apo E polymorphism on quantitative traits differ somewhat between Hispanics and non-Hispanic whites, this probably reflects the overall difference in frequencies of the less common alleles in the Hispanics rather than a biological difference in the effects of these alleles on lipid metabolism. |
| Impact of cholesterol depletion on shape changes, actin reorganization, and signal transduction in neutrophil-like HL-60 cells Niggli, V., A. V. Meszaros, et al. (2004), Exp Cell Res 296(2): 358-68. Abstract: Stimulation of neutrophils with chemotactic peptide induces actin reorganization, formation of actin-rich protrusions, and development of polarity. Shape changes and actin polymerization can also be induced by phorbol ester-mediated direct activation of protein kinase C (PKC). We have investigated the role of cholesterol in stimulus-dependent motile events and in activation of signaling pathways in neutrophil-like differentiated HL-60 cells. Depletion of plasma membrane cholesterol using methyl-beta-cyclodextrin (MbetaCD) prevented chemotactic peptide and phorbol ester-induced shape changes and increases in cytoskeletal actin. Cholesterol depletion almost completely suppressed chemotactic peptide-mediated activation of p42/44 mitogen-activated protein kinase (MAPK). Phosphorylation of protein kinase B on Thr-308, which is indicative of activation of phosphatidylinositol 3-kinase, was in contrast only partially inhibited. Stimulus-mediated membrane recruitment of different PKC isoforms was differentially affected by treatment of cells with MbetaCD. Membrane recruitment of PKCalpha induced by chemotactic peptide or phorbol ester was suppressed, whereas that of PKCbetaII was only partially affected. Membrane association of PKCdelta was almost insensitive to cholesterol depletion. In summary, our results implicate an important role of cholesterol-containing lipid microdomains (rafts) especially in chemotactic peptide-induced activation of MAPK pathways and in chemotactic peptide- and phorbol ester-mediated activation of PKCalpha. |
| Impact of cholesterol on cardiovascular morbidity and mortality in older adults Chen, Y. T. and H. M. Krumholz (1999), Nutrition 15(3): 242-4. |