| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of alkyl chain unsaturation and cholesterol intercalation on oxygen transport in membranes: a pulse ESR spin labeling study Subczynski, W. K., J. S. Hyde, et al. (1991), Biochemistry 30(35): 8578-90. Abstract: Transport and diffusion of molecular oxygen in phosphatidylcholine (PC)-cholesterol membranes and their molecular mechanism were investigated. A special attention was paid to the molecular interaction involving unsaturated alkyl chains and cholesterol. Oxygen transport was evaluated by monitoring the bimolecular collision rate of molecular oxygen and the lipid-type spin labels, tempocholine phosphatidic acid ester, 5-doxylstearic acid, and 16-doxylstearic acid. The collision rate was determined by measuring the spin-lattice relaxation times (T1's) in the presence and absence of molecular oxygen with long-pulse saturation-recovery ESR techniques. In the absence of cholesterol, incorporation of either a cis or trans double bond at the C9-C10 position of the alkyl chain decreases oxygen transport at all locations in the membrane. The activation energy for the translational diffusion of molecular oxygen in the absence of cholesterol is 3.7-6.5 kcal/mol, which is comparable to the activation energy theoretically estimated for kink migration or C-C bond rotation of alkyl chains Trauble, H. (1971) J. Membr. Biol. 4, 193-208; Pace, R. J., & Chan, S. I. (1982) J. Chem. Phys. 76, 4241-4247. Intercalation of cholesterol in saturated PC membranes reduces oxygen transport in the headgroup region and the hydrophobic region near the membrane surface but little affects the transport in the central part of the bilayer. In unsaturated PC membranes, intercalation of cholesterol also reduces oxygen transport in and near the headgroup regions. In contrast, it increases oxygen transport in the middle of the bilayer. On the basis of these observations, a model for the mechanism of oxygen transport in the membrane is proposed in which oxygen molecules reside in vacant pockets created by gauche-trans isomerization of alkyl chains and the structural nonconformability of neighboring lipids, unsaturated PC and cholesterol in particular, and oxygen molecules jump from one pocket to the adjacent one or move along with the movement of the pocket itself. The presence of cholesterol decreases oxygen permeability across the membrane in all membranes used in this work in spite of the increase in oxygen transport in the central part of unsaturated PC-cholesterol membranes because cholesterol decreases oxygen transport in and near the headgroup regions, where the major barriers for oxygen permeability are located. Oxygen gradients across the membranes of the cells and the mitochondria are evaluated. Arguments are advanced that oxygen permeation across the protein-rich mitochondrial membranes can be a rate-limiting step for oxygen consumption under hypoxic conditions in vivo. |
| Effect of allicin from garlic powder on serum lipids and blood pressure in rats fed with a high cholesterol diet Ali, M., K. K. Al-Qattan, et al. (2000), Prostaglandins Leukot Essent Fatty Acids 62(4): 253-9. Abstract: The use of fresh aqueous garlic extract is known to be effective in reducing thromboxane formation by platelets in both in vivo and in vitro animal models of thrombosis. In the present study, we studied the effect of Lichtwer garlic powder (containing 1.3% alliin equivalent to 0.6% allicin) on the serum cholesterol, triglyceride, glucose, protein, and systolic blood pressure in rats fed with a high cholesterol diet. Experimental rats were fed a 2% high cholesterol diet with and without garlic powder for 6 weeks. Control rats were fed a normal diet. The aqueous garlic powder extract was given orally to rats on a daily basis. It was observed that cholesterol-fed animals had a significant increase in serum cholesterol compared to the control group of rats fed on a normal diet. However, when the rats were fed with a high cholesterol diet mixed with garlic powder, there was a significant reduction in their serum cholesterol levels compared with the group which were on a diet containing high cholesterol without garlic powder. Serum triglyceride levels were also significantly lowered by garlic powder when compared to control and high cholesterol diet group rats. The blood pressure of the high cholesterol diet animals was significantly higher compared to the animals receiving the control diet. The blood pressure of the animals receiving garlic powder and high cholesterol diet was significantly lower as compared to the high cholesterol and control diet group. No significant changes were observed in the serum glucose and protein in all of the rats. These results show that garlic is beneficial in reducing blood cholesterol, triglycerides levels and systolic blood pressure in hypercholesterolemic rats. Our experimental results show that garlic may beneficially affect two risk factors for atherosclerosis--hyperlipidemia and hypertension. |
| Effect of alterations of blood cholesterol levels on macrophages in the myocardium of New Zealand White rabbits Kinscherf, R., H. Kamencic, et al. (1997), J Leukoc Biol 62(6): 719-25. Abstract: We investigated the effect of alterations of blood cholesterol levels on macrophages (mphi) in the myocardium of New Zealand White (NZW) rabbits. Three groups of NZW rabbits were used: controls, rabbits fed a 0.5% cholesterol-enriched diet (CH-D) for 96 days, and rabbits fed a 0.5% CH-D for 96 days followed by normal chow for 4 months. Immunohistochemical analysis by mAbs directed against mphi (RAM-11) and Mn superoxide dismutase (MnSOD) were quantified by computer-assisted morphometry. Using cultured human and rabbit mphi, a cross-reaction of the human MnSOD mAbs was found as well as the predominant localization of MnSOD-immunoreactivity (IR) in mitochondria. In group 1, only a very few RAM-11-immunoreactive (ir) mphi occurred in the interstitial space of the myocardium. In group II blood cholesterol levels significantly increased in parallel with the numbers of mphi, which often contained lipid droplets (foam cells). Although blood cholesterol concentrations regressed about 10-fold in group III, mphi in the myocardium were found to be reduced only about 20%. Most mphi were also MnSOD-ir. In atherosclerotic coronary arteries RAM-11-IR was located in mphi and also extracellularly, whereas MnSOD-IR was found only in mphi. Drastically induced MnSOD in the mitochondria of mphi is suggested as an indicator of increased oxidative stress caused by in vitro conditions or by phagocytosis of low-density lipoprotein in vivo. Elevation of the cholesterol level leads to a long-term increase and its regression results in a delayed reduction of such mphi, which seem to play a key role in the atherogenesis of the coronary arteries as well. |
| Effect of an arginine-rich amphipathic helical peptide on plasma cholesterol in dyslipidemic mice Garber, D. W., S. Handattu, et al. (2003), Atherosclerosis 168(2): 229-37. Abstract: We have shown that the dual domain peptide Ac-hE18A-NH(2), in which LRKLRKRLLR, (141-150 region of human apo E) covalently linked to a class A lipid-associating domain, is able to associate with apo B-containing lipoproteins and enhance their clearance both in vitro and in vivo. We present here the differential effects of this peptide on the plasma cholesterol levels in different mouse models. The peptide intravenously administered (100 microg) into C57BL/6J mice on atherogenic diet, apo E null, and apo E null/LDL-receptor (LDL-R) null double knock out mouse models, was able to rapidly reduce plasma cholesterol levels within 2 min, and the effect persisted for more than 6 h. The reduction was limited to the VLDL and IDL/LDL fractions; HDL was not reduced in any mouse model studied. However, the peptide had no effect on the plasma cholesterol levels in C57BL/6J mice on normal diet, LDL-R null mice on normal chow, and LDL-R null mice on Western diet. Administration to LDL-R null mice of 125I-labelled human lipoproteins incubated with peptide resulted in accelerated human VLDL and LDL clearance with associated increase of radioactivity in the liver. These results, coupled with our earlier in vitro observations, indicate that the Arg-rich peptide-assisted rapid clearance of plasma cholesterol in dyslipidemic mice is due to the peptide targeting apo B-48-containing atherogenic lipoproteins to the liver for increased uptake and degradation. |
| Effect of an atherogenic diet on lipoprotein cholesterol profile in the F1B hybrid hamster de Deckere, E. A., N. J. de Fouw, et al. (1993), Atherosclerosis 103(2): 291-4. |
| Effect of an extract containing esterol on plasma cholesterol and oxidants Levy, Y., E. Paster, et al. (1998), Harefuah 134(6): 449-51, 503, 502. Abstract: 16 patients with hypercholesterolemia were treated with an extract of alpha-alpha leaves (esterol) while on a low-fat, low-cholesterol diet. Esterol is believed to inhibit the absorption of cholesterol and bile acids and may interfere with the absorption of essential nutrients. As oxidative modification of lipoproteins is required for the process of atherosclerosis, plasma antioxidant vitamins were followed. After 4 months of treatment, plasma cholesterol decreased by 10% from 282 to 250 mg/dl (p < 0.001) and LDL cholesterol by 13%, from 203 to 177 mg/dl (p < 0.001). Plasma antioxidant vitamins E, A and beta-carotene were unchanged. Thus, esterol has a cholesterol-lowering effect but apparently does not lower fat-soluble, plasma antioxidant vitamins. Both cholesterol-lowering and plasma antioxidant vitamins are important for the primary prevention of coronary artery disease in hypercholesterolemia. |
| Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol Irace, C., G. Mancuso, et al. (2004), Atherosclerosis 177(1): 113-8. Abstract: It has been recently hypothesized that both TNFalpha and anti TNFalpha treatment have a stimulating effect on nitric oxide synthesis and release. Moreover, an in vitro experiment has demonstrated that HDL-cholesterol binds TNFalpha. Aims of our study were to investigate wall shear stress of peripheral arteries and endothelial function of brachial artery in subjects with Rheumatoid Arthritis (RA) at baseline and after infliximab. Moreover, we evaluated the effect of anti TNFalpha therapy on lipid profile. Ten patients with RA received infliximab therapy at weeks 0, 2 and 6. Lipids and vascular parameters were measured before and the day after each infusion. After the first treatment, FMD increased (3.7 +/- 1.9% versus 17.5 +/- 2.9%, P <0.01) and common carotid and brachial artery diameters decreased (5.9 +/- 0.2 mm versus 5.5 +/- 0.2 mm; 3.5 +/- 0.4 mm versus 3.1 +/- 0.4 mm, respectively, P <0.005). Common carotid and brachial artery wall shear stress increased (21.1 +/- 1.1 dynes/cm2 versus 23.9 +/- 1.4 dynes/cm2; 42.0 +/- 4.7 dynes/cm2 versus 51.6 +/- 5.7 dynes/cm2, P <0.01). Similar results were observed after the second and third infusion. All these parameters returned to pre-treatment level at the following infusion. HDL-cholesterol and apolipoprotein AI significantly decreased after each treatment (1st treatment: 1.4 +/- 0.05 mmol/L versus 1.2 +/- 0.06 mmol/L, P <0.01; 1.73 +/- 0.05 g/L versus 1.57 +/- 0.02 g/L, P <0.03). The present data show vasoconstriction and an increase of wall shear stress in studied arteries after infliximab. HDL cholesterol is reduced by treatment and does not seem to influence FMD. |
| Effect of antiatherogenic L-aspartate and L-glutamate on serum lipoproteins cholesterol and apolipoproteins A-1 and B in rabbits fed with high cholesterol diet Yanni, A. E., D. N. Perrea, et al. (2005), Nutr Metab Cardiovasc Dis 15(3): 161-5. Abstract: BACKGROUND AND AIM: It has been shown that aspartate and glutamate inhibit mononuclear cell adhesion to the endothelium and formation of foam cells in the intima of thoracic aorta in cholesterol-fed rabbits. The purpose of the present study was to investigate whether a high cholesterol diet supplemented with aspartate and glutamate may alter lipoproteins cholesterol and apolipoproteins A-1 and B levels in rabbits. METHODS AND RESULTS: Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-1 (apoA-1), apolipoprotein B (apoB), atherogenic index (AI) and apoA-1/apoB ratio were determined in 17 male New Zealand white rabbits fed a cholesterol plus corn oil diet (control group) or the same diet supplemented with aspartate and glutamate (Asp+Glu group) for 4 weeks. Both diets were found to increase TC, LDL-C, apoB and AI, while apoA-1/apoB ratio was decreased compared to baseline values. TG did not seem to be affected in the 4 weeks time in both groups. There was a significant increase of HDL-C in Asp+Glu group and a marked decrease of apoA-1 in control group during the study. CONCLUSIONS: Oral administration of aspartate and glutamate has been shown to inhibit fatty streak initiation in cholesterol-fed rabbits. The two amino acids did not have any effect on serum TC, LDL-C, TG and apoB concentrations. However, they increased HDL-C and maintained apoA-1 levels. Their antiatherogenic effect probably may be explained by different mechanisms than these related to the atherogenic lipids lowering, and it is possible to involve HDL-C and apoA-1. |
| Effect of antibiotics as cholesterol-lowering agents Jenkins, D. J., C. W. Kendall, et al. (2005), Metabolism 54(1): 103-12. Abstract: Antibiotics were once proposed as hypercholesterolemic agents although the mechanism is unclear, despite broad implications, including providing an alternative approach to cholesterol reduction, with potential relevance for current trials of antibiotics to reduce cardiovascular disease, and possible confounding of routine diagnostic cholesterol measurements. The effect on serum lipids of antibiotics against aerobes and anaerobes, together with possible mechanisms, was therefore explored. Twenty-two men and women took antibiotics for 10 days (either ciprofloxacin for 13 subjects or metronidazole for 10 subjects), with 10 days control in random order separated by 2-week washout periods. Subjects maintained low-fat diets throughout the study. Blood samples and blood pressure were obtained on days 0 and 10 of each phase with 3-day fecal collections and 12-hour breath gas collections at the end of each phase. The results indicated that metronidazole markedly reduced low-density lipoprotein cholesterol (-14.0 +/- 4.0%, P =.006), oxidized low-density lipoprotein (-23.0 +/- 5.1%, P =.002), and the apolipoprotein B/A-I ratio (-18.0 +/- 2.8%, P <.001), whereas the reduction with ciprofloxacin was less pronounced (apolipoprotein B/A-I, -5.0 +/- 1.8%, P =.017). Neither antibiotic altered C-reactive protein or blood pressure. The low-density lipoprotein cholesterol reduction related to an increase in bifidobacteria (r = -0.46, P =.029), but not to markers of colonic fermentation. We conclude that antibiotics can reduce serum lipids acutely. These effects may confound diagnostic measurements but indicate possible links between colonic microflora and blood lipids and the need to study ways of altering colonic microflora by nonantibiotic means as a potential therapeutic option. |
| Effect of antimicrobials on cholesterol synthesis and content in liver and small intestines Pugalendhi, K. V., P. R. Sudhakaran, et al. (1992), Indian J Exp Biol 30(2): 152-4. Abstract: The antimicrobials tetracycline, ampicillin and bactrim (cotrimoxazole) decreased HMG CoA reductase activity in liver and small intestines of albino rats. Diminished incorporation of 1, 2, 14C acetate into cholesterol of small intestines in bactrim group was noted. There was a significant fall in cholesterol content of liver, duodenum, jejunum and ileum of the bactrim group and jejunum only in tetracycline group. |
| Effect of antioxidant protection by p-coumaric acid on low-density lipoprotein cholesterol oxidation Zang, L. Y., G. Cosma, et al. (2000), Am J Physiol Cell Physiol 279(4): C954-60. Abstract: Mechanisms in which p-coumaric acid (CA) acts as an antioxidant are not well understood. This study investigated whether CA can act as a direct scavenger of reactive oxygen species (ROS) and whether it minimizes the oxidation of low-density lipoprotein (LDL). Rats were administered CA in drinking water at low or high doses for 10, 21, and 30 days (uptakes were 29 and 317 mg/day, respectively). Blood levels of 8-epiprostaglandin F(2alpha) were monitored as a marker of LDL oxidation. Oral administration of CA (317 mg/day) for 30 days significantly inhibited LDL oxidation. CA also reduced LDL cholesterol levels in serum but had no effect on levels of high-density lipoprotein cholesterol. In vitro studies that used electron spin resonance in combination with spin trapping techniques were used to determine the ability of CA to scavenge ROS and alter LDL oxidation. CA effectively scavenged.OH in a dose-dependent manner. IC(50) and maximum velocity for CA scavenging of.OH were 4. 72 microM and 1.2 microM/s, respectively, with a rate constant of 1. 8 x 10(11) M(-1). s(-1). Our studies suggest that the antioxidant properties of CA may involve the direct scavenging of ROS such as.OH. |
| Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits Sugano, M., N. Makino, et al. (1998), J Biol Chem 273(9): 5033-6. Abstract: Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins. However, the exact role of CETP in the development of atherosclerosis has not been determined. In the present study, we examined the effect of the suppression of increased plasma CETP by intravenous injection with antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the development of atherosclerosis in rabbits fed a cholesterol diet. The ODNs against rabbit CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method to regulate liver gene expression. Twenty-two male Japanese White rabbits were used in the experiment. Eighteen animals were fed a standard rabbit chow supplemented with 0.3% cholesterol throughout the experiment for 16 weeks. At 8 weeks, they were divided into three groups (six animals in each group), among which the plasma total and HDL cholesterol concentrations did not significantly change. The control group received nothing, the sense group were injected with the sense ODNs complex, and the antisense group were injected with the antisense ODNs complex, respectively, for subsequent 8 weeks. ASOR. poly(L-lysine) ODNs complex were injected via the ear veins twice a week. Four animals were fed a standard rabbit diet for 16 weeks. The total cholesterol concentrations and the CETP mass in the animals injected with antisense ODNs were all significantly decreased in 12 and 16 weeks compared with those injected with sense ODNs and the control animals. The HDL cholesterol concentrations measured by the precipitation assay did not significantly change among the groups fed a cholesterol diet, and triglyceride concentrations did not significantly change in the four groups. However, at the end of the study, when the HDL cholesterol concentrations were measured after the isolation by ultracentrifugation and a column chromotography, they were significantly higher in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. A reduction of CETP mRNA and an increase of LDL receptor mRNA in the liver were observed in the animals injected with antisense ODNs compared with those injected with sense ODNs and the control animals. Aortic cholesterol contents and the aortic percentage lesion to total surface area were significantly lower in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. These findings showed for the first time that suppression of increased plasma CETP by the injection with antisense ODNs against CETP coupled to ASOR carrier molecules targeted to the liver could thus inhibit the atherosclerosis possibly by decreasing the plasma LDL + very low density lipoprotein (VLDL) cholesterol in cholesterol-fed rabbits. |
| Effect of apolipoprotein activators on the specificity of lecithin:cholesterol acyltransferase: determination of cholesteryl esters formed in A-I/C-III deficiency Subbaiah, P. V., R. A. Norum, et al. (1991), J Lipid Res 32(10): 1601-9. Abstract: Although it is known that plasma lecithin:cholesterol acyltransferase (LCAT) is activated by several apolipoproteins (apo) including A-I, C-I, D, A-IV, and E, it is not clear what the physiological importance of having different apolipoprotein activators is. One possible explanation is that the activation by different apolipoproteins may result in the utilization of different species of phosphatidylcholine (PC), leading to the formation of different species of cholesteryl esters (CE). In order to determine this possibility, we analyzed the molecular species composition of PC and CE in two patients with familial deficiency of apoA-I and apoC-III. The LCAT activity, assayed by three different procedures, was found to be 36-63% of the control value. The lower LCAT activity, however, was due to deficiency of the enzyme rather than the absence of apoA-I. The patients' plasma was relatively enriched with sn-2 18:2 PC species reflecting the partial deficiency of LCAT activity. The fatty acid composition of plasma CE was not significantly different from that of controls. HPLC analysis of labeled CE formed after incubation of plasma with C14cholesterol showed no significant difference in the species of CE synthesized by the LCAT reaction. The transfer of pre-existing as well as newly formed CE from HDL to the apoB-containing lipoproteins was accelerated compared to control plasma. These results show that the absence of apoA-I does not significantly affect either the activity or the specificity of LCAT, and that the other apolipoprotein activators can substitute adequately for it. |
| Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma Parks, J. S., H. Li, et al. (1995), J Lipid Res 36(2): 349-55. Abstract: Plasma cholesteryl ester (CE) synthesis by lecithin cholesterol acyltransferase (LCAT) is activated by apolipoprotein (apo)A-I. We studied the effect of plasma apoA-I concentration on LCAT activation, using normal, heterozygous or homozygous apoA-I-deficient mice made by gene targeting. Plasma esterified cholesterol concentrations of mice fed chow diets were ordered (mean +/- SEM): 105 +/- 7 (normal) > 70 +/- 5 (heterozygotes) > 26 +/- 2 (homozygotes) mg/dl. Plasma free cholesterol concentrations were similar among the three genotypes. Endogenous LCAT activity, measured as the decrease in plasma free cholesterol after a 1 h incubation at 37 degrees C, was ordered: 44 +/- 3 (normal) > 21 +/- 2 (heterozygotes) > 5 +/- 1 (homozygotes) nmol CE formed/h per ml plasma. Using a recombinant exogenous substrate consisting of egg yolk phospholipid, 14Ccholesterol, and apoA-I, CE formation of normals and heterozygotes was similar (27.4 +/- 0.6 and 28.8 +/- 1.3 nmol/h per ml plasma, respectively), but was significantly less for homozygotes (19.2 +/- 1.7 nmol/h per ml plasma). However, using a small unilamellar vesicle substrate particle containing phospholipid and 14Ccholesterol, CE formation was ordered: 1.6 +/- 0.1 (normal) = 1.6 +/- 0.1 (heterozygotes) > 0.6 +/- 0.1 (homozygotes) nmol/h per ml plasma; addition of apoA-I to the plasma of homozygous animals restored CE formation to normal levels (1.6 +/- 0.1). CE fatty acid analysis demonstrated that plasma from homozygous mice contained significantly more saturated and monounsaturated and fewer polyunsaturated fatty acids compared to normal and heterozygous mice.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effect of apolipoprotein A-I on ATP binding cassette transporter A1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells Tang, C. K., G. H. Tang, et al. (2004), Acta Biochim Biophys Sin (Shanghai) 36(3): 218-26. Abstract: Cholesterol-loaded macrophage foam cells are a central component of atherosclerotic lesions. ATP binding cassette transporter A1 (ABCA1), the defective molecule in Tangier disease, mediates the efflux of phospholipid and cholesterol from cells to apolipoprotein A-I (apoA-I), reversing foam cell formation. This study investigated the effect of apoA-I on ABCA1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells. After exposure of the cultured THP-1 macrophage-derived foam cells to apoA-I for different time, cholesterol efflux, ABCA1 mRNA and protein levels were determined by FJ-2107P type liquid scintillator, RT-PCR and Western blot, respectively. The mean ABCA1 fluorescence intensity on THP-1 macrophage-derived foam cells was detected by flow cytometry. Results showed that apoA-I markedly increased ABCA1-mediated cholesterol efflux from THP-1 macrophage-derived foam cells. This was accompanied by an increase in the content of ABCA1. ApoA-I did not alter ABCA1 mRNA abundance. Significantly, thiol protease inhibitors increased the level of ABCA1 protein and slowed its decay in THP-1 macrophage-derived foam cells, whereas none of the proteosome-specific inhibitor lactacystin, other protease inhibitors, or the lysosomal inhibitor NH4Cl showed such effects. The apoA-I-mediated cellular cholesterol efflux was enhanced by thiol protease inhibitors. Our results suggested that thiol protease inhibitors might provide an alternative way to upregulate ABCA1 protein. This strategy is especially appealing since it may mimic the stabilizing effect of the natural ligands apoA-I. |
| Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans Weinberg, R. B., B. W. Geissinger, et al. (2000), J Lipid Res 41(12): 2035-41. Abstract: We investigated the effect of the A-IV-2 allele, which encodes a Q360H substitution in apolipoprotein (apo) A-IV, and dietary fat on cholesterol absorption in humans. In three separate studies we compared fractional intestinal cholesterol absorption between groups of subjects heterozygous for the A-IV-2 allele (1/2) and homozygous for the common allele (1/1) receiving high cholesterol (approximately 800 mg/day) diets with different fatty acid compositions. All subjects had the apoE 3/3 genotype. There was no difference in cholesterol absorption between the two genotype groups receiving a high saturated fat diet (33% of total energy as fat; 18% saturated, 3% polyunsaturated, 12% monounsaturated) or a low fat diet (22% of total energy as fat; 7% saturated, 7% polyunsaturated, 8% monounsaturated) diet. However, on a high polyunsaturated fat diet (32% of total energy as fat; 7% saturated, 13% polyunsaturated, 12% monounsaturated) mean fractional cholesterol absorption was 56. 7% +/- 1.9 in 1/1 subjects versus 47.5% +/- 2.1 in 1/2 subjects (P = 0.004). A post hoc analysis of the effect of the apoA-IV T347S polymorphism across all diets revealed a Q360H x T347S interaction on cholesterol absorption, and suggested that the A-IV-2 allele lowers cholesterol only in subjects with the 347 T/T genotype.We conclude that a complex interaction between apoA-IV genotype and dietary fatty acid composition modulates fractional intestinal cholesterol absorption in humans. |
| Effect of apolipoprotein E phenotype on diet-induced lowering of plasma low density lipoprotein cholesterol Lopez-Miranda, J., J. M. Ordovas, et al. (1994), J Lipid Res 35(11): 1965-75. Abstract: The National Cholesterol Education Program (NCEP) has recommended that dietary total fat, saturated fat, and cholesterol intake be reduced to < or = 30% of calories, < 10% of calories, and < 300 mg/day, respectively (Step 1 diet) in the general population to reduce plasma low density lipoprotein (LDL) cholesterol levels and heart disease risk. We examined the LDL cholesterol-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/day of cholesterol) as compared to an average American diet (39% fat, 15% saturated fat, and 435 mg/day of cholesterol) in 128 subjects using diet periods of 4-24 weeks for each diet phase. The mean LDL cholesterol reduction was 15% in males (n = 83) and 8% in post-menopausal females (n = 45). The effect of apolipoprotein (apo) E phenotype on responsiveness was examined. LDL cholesterol lowering in males was 14% for 60 apoE3/3 subjects, 23% for 10 apoE3/4 subjects, and 16% for 13 apoE3/2 subjects. Male apoE3/4 subjects had a significantly greater LDL cholesterol reduction (P = 0.006) and a greater decrease in the LDL/HDL ratio (P = 0.047) than apoE3/3 subjects. In females, 7% lowering in LDL cholesterol was observed in 34 apoE3/3 subjects and 11% lowering was observed in 7 apoE3/4 subjects (P = 0.12). A meta-analysis of data from published studies supports this conclusion. These data indicate that apoE phenotype modulates the LDL cholesterol-lowering response to a diet meeting NCEP Step 1 criteria, and that male subjects carrying the apoE4 allele are more responsive than other subjects. |
| Effect of apolipoprotein E polymorphism on bile lipid composition and the formation of cholesterol gallstone Hasegawa, K., S. Terada, et al. (2003), Am J Gastroenterol 98(7): 1605-9. Abstract: OBJECTIVE: It remains a matter of controversy whether possession of the apolipoprotein E4 (apoE4) allele is a genetic risk factor for the formation of cholesterol gallstones. The aim of the present study was to test this hypothesis by investigating the effect of apoE4 on bile lipid composition in normal subjects and in patients with cholesterol gallstones and to evaluate the distributions of apoE alleles in these two groups. METHODS: The study population consisted of 79 patients who underwent open or laparoscopic cholecystectomy for symptomatic cholesterol gallstone disease. The control group (n = 53) included 11 patients with benign gallbladder polyps and 42 normal subjects acting as donors in living donor liver transplantation. The apoE genotypes were assessed by dot blot hybridization with digoxigenin-labeled probes. Bile lipid composition was determined by enzymatic assays and high performance liquid chromatography. RESULTS: Bile lipid composition and cholesterol saturation index (CSI) were similar in the control subjects harboring the apoE4 allele and those without apoE4 (mean CSI, 85.9% and 72.2%, respectively, p = 0.69). Likewise, in the cholesterol gallstone patients, bile lipid composition and CSI were similar in the patients with and without apoE4 allele (mean CSI, 134.9% vs 152.2%, p = 0.6). Furthermore, the prevalence of the apoE4 allele was similar in the patients with cholesterol gallstones and in the control group (8.5% vs 7.6%, p = 0.46, OR = 0.88; 95% CI = 0.64-1.22). CONCLUSIONS: The apoE4 allele is not a contributory factor to cholesterol gallstone formation, at least in the Japanese population. |
| Effect of apolipoprotein E polymorphism on serum lipid response to the separate modification of dietary fat and dietary cholesterol Sarkkinen, E., M. Korhonen, et al. (1998), Am J Clin Nutr 68(6): 1215-22. Abstract: BACKGROUND: The magnitude of the influence of the apolipoprotein (apo) E genotype on the lipid response to different cholesterol-lowering diet modifications has been controversial. OBJECTIVE: The aim of the study was to investigate the effect of apo E genotype on serum lipid response to the separate modification of dietary fat and cholesterol. DESIGN: A prospective study design with the 3 main apo E genotype groups (3/3, 3/4, and 4/4; n = 15 in each group) was used. Groups were matched for sex, age, body mass index, menopausal status, and baseline serum cholesterol concentration. Subjects followed 3 different diets in fixed order: 1) a standardized baseline diet (38% fat, 300 mg cholesterol/d), 2) a modified National Cholesterol Education Program (NCEP) diet (34% fat, 265 mg cholesterol/d), and 3) the modified NCEP diet + cholesterol (566 mg cholesterol/d). Subjects were middle-aged (50.9 +/- 8.0 y) and mildly hypercholesterolemic (6.55 +/- 1.05 mmol/L). RESULTS: The genotype groups differed in their total cholesterol response to the NCEP diet; the mean (95% CI) decrease being greatest, -14.1% (-19.8%, -8.6%), in subjects with apo E genotype 4/4 (P = 0.03, analysis of variance). The increase in total cholesterol after addition of 300 mg cholesterol was also greatest in subjects with apo E 4/4 10.4% (5.8%, 15.1%) (P = 0.03, analysis of variance). CONCLUSIONS: Apo E genotype modified the lipid response to changes in both dietary fat and cholesterol in mildly hypercholesterolemic subjects; the response was greatest in subjects with apo E genotype 4/4 and even a moderate increase in dietary cholesterol resulted in a 10% elevation in serum total cholesterol in them. |
| Effect of apolipoprotein E4 allele on plasma LDL cholesterol response to diet therapy in type 2 diabetic patients Saito, M., M. Eto, et al. (2004), Diabetes Care 27(6): 1276-80. Abstract: OBJECTIVE: The aim of this study was to investigate the effect of apolipoprotein (apo)E4 allele on plasma LDL cholesterol response to calorie-restricted diet therapy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Twenty-four diabetic patients with the apoE3/3 genotype and 11 diabetic patients with the apoE4/3 genotype were recruited. Participants were hospitalized for calorie-restricted diet therapy (25.0 kcal. kg body wt(-1). day(-1)) for 14 days. Body weight, fasting plasma glucose (FPG) levels, and plasma lipid levels on hospital days 1 and 14 were compared between the two apoE genotype groups. RESULTS: There were no significant differences in baseline FPG levels, HbA(1c) levels, BMI, and plasma levels of total cholesterol, triglyceride, and HDL cholesterol between the two apoE genotype groups, but baseline plasma levels of LDL cholesterol were significantly higher in the apoE4/3 group than in the apoE3/3 group. Body weight decreased slightly and FPG levels decreased significantly after diet therapy in both apoE genotype groups. In the apoE3/3 group, only plasma levels of triglyceride decreased significantly after diet therapy, whereas in the apoE4/3 group, plasma levels of triglyceride, total cholesterol, and LDL cholesterol decreased significantly after diet therapy. The decrease (percentage of change) in total cholesterol (-16.3 vs. -6.6%) and LDL cholesterol (-15.6 vs. -0.7%) after diet therapy was significantly greater in the apoE4/3 group than in the apoE3/3 group. CONCLUSIONS: Calorie-restricted diet therapy is more effective in reducing plasma LDL cholesterol in type 2 diabetic patients with the apoE4 allele. |