| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of the surface lipid composition of reconstituted LPA-I on apolipoprotein A-I structure and lecithin: cholesterol acyltransferase activity Sparks, D. L., P. G. Frank, et al. (1998), Biochim Biophys Acta 1390(2): 160-72. Abstract: Characterization of the factors that regulate plasma cholesterol esterification shows that the increased activity of lecithin:cholesterol acyltransferase (LCAT) in the plasma of hyperlipidemic subjects is due to enhanced interactions with a preferred substrate. The details of how the physical properties of high density lipoproteins (HDL) may affect their ability to stimulate cholesterol esterification by LCAT have been investigated in homogeneous reconstituted HDL particles containing two molecules of apolipoprotein (apo) A-I (Lp2A-I) and palmitoyl-oleoyl phosphatidylcholine (POPC). Increasing the POPC or sphingomyelin (SPH) content in an Lp2A-I complex increases particle size and stability but decreases the negative surface charge of apoA-I. Increasing Lp2A-I POPC or SPH content also significantly inhibits cholesterol esterification by LCAT. Increase in the maximum rate of CE production (Vmax) by LCAT is directly related to an increased negative charge on the different Lp2A-I particles and to a reduced amount and stability of amphipathic alpha-helices in apoA-I. In contrast, increasing the Lp2A-I complex negative charge directly by addition of a charged lipid, phosphatidylinositol (PI), has minimal effect on apoA-I conformation and LCAT activation. While variations in Lp2A-I PI content have little effect on the interfacial binding of LCAT, increasing POPC content appears to directly increase the binding affinity of LCAT for the different Lp2A-I particles. These results show that LCAT is stimulated by an apoA-I conformation-dependent increase in negative charge but is less sensitive to electrostatic changes in the lipid interface of discoidal Lp2A-I. The activation of LCAT appears to be dependent on the exposure of both central (residues 98-132) and N-terminal (residues 2-8) domains in apoA-I. A strong relationship between the immunoreactivity of two specific mAbs, 4H1 and A11, and LCAT reactivity suggests that the N-terminus of apoA-I may interact with a central domain in a manner that may regulate the accessibility of LCAT to the edge of the disc. This indicates that the conformation and charge of apoA-I are sensitive to the surface-lipid composition of HDL particles and play a central role in regulating LCAT activation. Since alterations in the surface lipid composition of HDL particles from hyperlipidemic subjects also modify the charge and structure of these particles, this may stimulate the rates of cholesterol esterification by making these lipoproteins preferred LCAT substrates. |
| Effect of the type of dietary fat on biliary lipid composition and bile lithogenicity in humans with cholesterol gallstone disease Yago, M. D., V. Gonzalez, et al. (2005), Nutrition 21(3): 339-47. Abstract: OBJECTIVE: The effect of the type of dietary fat on bile lipids and lithogenicity is unclear. This study compared the effects of two dietary oils that differed in fatty acid profile on biliary lipid composition in humans. METHODS: Female patients who had cholesterol gallstones and were scheduled for elective cholecystectomy were studied. For 30 d before surgery, subjects were kept on diets that contained olive oil (olive oil group, n = 9) or sunflower oil (sunflower oil group, n = 9) as the main source of fat. Gallbladder bile and stones were sampled at surgery. After cholecystectomy, duodenal samples were collected by nasoduodenal intubation during fasting and after administration of mixed liquid meals that included the corresponding dietary oil. Duodenal and gallbladder bile samples were analyzed for cholesterol, phospholipids, and total bile acids by established methods. Individual bile acid conjugates in gallbladder bile were measured by high-performance liquid chromatography. Gallstones were analyzed by semiquantitative polarizing light microscopy. RESULTS: Despite marked differences in the absolute concentration of biliary lipids and total lipid content, manipulation of dietary fat ingestion did not influence the cholesterol saturation or the profile of individual bile acids in gallbladder bile obtained from patients who had gallstones. All but one subject had mixed cholesterol stones. A cholesterol saturation index of hepatic bile in fasted cholecystectomized patients was similar in both dietary groups and indicative of supersaturation. In response to the test meal, the cholesterol saturation index decreased significantly in patients given the olive oil diet, reaching values lower than one at 120 min postprandially. In contrast, hepatic bile secreted by patients who consumed sunflower oil appeared supersaturated (cholesterol saturation index >1.5) throughout the experiment. CONCLUSIONS: Our results suggest that the type of dietary fat habitually consumed can influence bile composition in humans. In gallbladder, this influence was noted in the presence of more concentrated bile in the olive oil group. However, this was not translated into a modification of cholesterol saturation, which is likely due to the fact that cholesterol gallstones were present by the time the dietary intervention started. The finding that a typical postprandial variation in hepatic bile lithogenicity occurred only in olive oil patients was revealing. While keeping in mind the methodologic limitations of this part of the study, some gastrointestinal and metabolic mechanisms for this effect are discussed. |
| Effect of time between measurements on within-subject variability for total cholesterol and high-density lipoprotein cholesterol in women Choudhury, N., P. M. Wall, et al. (1994), Clin Chem 40(5): 710-5. Abstract: A single blood cholesterol measurement may not accurately reflect an individual's true mean concentration. If duplicate blood samples are taken, what number of days between sampling gives the best chance of detecting the maximum within-subject variation? In this study, we analyzed 20 serial blood samples obtained from each of 13 healthy, menstruating women over 35 days. Variability was calculated as the semivariogram, which gives the average squared difference between replicate samples taken over a range of sampling intervals. Data were available for a complete set of intervals from 1 to 26 days. Variability in total cholesterol (TC) increased as the interval between sampling increased from 1 to 12 days. With high-density lipoprotein cholesterol (HDL-C), variability increased from 1- to 7-day intervals. In practice, our results suggest that, irrespective of the time of menstruation, the minimal interval for collecting a second blood sample for TC and HDL-C assays is approximately 2 weeks. |
| Effect of trandolapril on vascular responsiveness in cholesterol-fed rabbit-isolated arteries Sanz, M., P. Ganado, et al. (2000), Eur J Pharmacol 397(2-3): 359-65. Abstract: According to the World Health Organisation, cardiovascular disorders are one of the main causes of morbi/mortality in the western world. The effect of trandolapril (0.3 mg kg(-1) day(-1)), a non-sulphydryl angiotensin-converting enzyme (ACE) inhibitor, on the vascular responsiveness in aorta isolated from hypercholesterolemic rabbits was examined. Three groups of rabbits (n=30) were used: Group 0 (control group); Group 1 (hypercholesterolemic group, 0.5% (wt/wt) cholesterol-enriched diet) and Group 2 (hypercholesterolemic+trandolapril 0.3 mg kg(-1) day(-1)). After 18 weeks of treatment, the rabbits were killed and the thoracic aorta, proximal coronary and mesenteric (5th branch) arteries were isolated, cleaned off and mounted in an organ bath. Trandolapril had no significant effect on plasma cholesterol, high density lipoprotein (HDL) or low density lipoprotein (LDL). Despite the lack of effect of the drug on the above-mentioned parameters, treatment with trandolapril improved endothelium-dependent relaxation induced by acetylcholine in aortic and mesenteric rings from hypercholesterolemic rabbits treated with trandolapril. The relaxation induced by 10(-5) M acetylcholine were 65.0+/-4.0%; 24. 0+/-9.4% (P<0.01, n=10) and 51.3+/-7.0% (P<0.01, n=10) in aortic rings from Groups 0, 1 and 2, respectively, and 50.0+/-12.0%; 10. 1+/-10.0% (P<0.01, n=10); 61.0+/-9.7% (P<0.01, n=10) in small mesenteric rings from Groups 0, 1 and 2, respectively. In addition, trandolapril treatment improved the increase in serotonin-induced contraction in proximal coronary arteries with respect to the hypercholesterolemic group. On the other hand, we did not find any differences among the group in endothelium-independent relaxation induced by sodium nitroprusside. These results provide evidence that trandolapril restores endothelium-dependent relaxation in hypercholesterolemic rabbit-isolated arteries. These data suggest that trandolapril might have beneficial action in the prevention of vascular alteration involved in atherosclerosis. |
| Effect of transforming growth factor beta-1 on the cholesterol side-chain cleavage system in the adrenal gland of sheep fetuses and newborns Naaman-Reperant, E., D. B. Hales, et al. (1996), Endocrinology 137(3): 886-92. Abstract: The present work examined the effect of transforming growth factor-beta1 (TGFbeta1) on the cholesterol side-chain cleavage system of sheep fetal and neonatal adrenal glands. Freshly isolated fetal adrenal cells produced 3-fold less pregnenolone from 22R- hydroxycholesterol than neonatal cells. Also, the relative amounts of immunoreactive cytochrome P450 side-chain cleavage (P450scc), adrenodoxin, and adrenodoxin reductase were 1.5- to 2-fold lower in mitochondria from fetal than neonatal cells. However, during culture under control conditions, the cholesterol side-chain cleavage activity and the amounts of P450scc, adrenodoxin, and adrenodoxin reductase of fetal cells increased after 48 h to reach neonatal values. A 5-day treatment with TGFbeta1 (1ng/ml) decreased significantly both the cholesterol side-chain cleavage activity and the amounts of immunoreactive P450scc, adrenodoxin, and adrenodoxin reductase in sheep fetal and neonatal adrenal cells in culture. Immunoreactive TGFbeta1- like material was present in freshly isolated adrenal cells from both fetuses and newborn lambs. After 2 days of culture, the amount of TGFbeta1-like protein was 2-fold lower than in freshly isolated fetal cells. No change was observed for neonatal cells. Finally, TGFbeta1 encoding messenger RNAs and TGFbeta-like immunoreactive protein were much higher in adrenal cortices from fetuses than from neonates. Taken together, these results have made TGFbeta1 a potentially attractive candidate for being an auto/paracrine negative regulator of the cholesterol side-chain cleavage system in the sheep fetal adrenal gland. |
| Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis in human hepatoma cell line Hep G2 Corsini, A., P. Grignaffini, et al. (1993), Cytotechnology 11 Suppl 1: S15-7. Abstract: The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake and degradation of 125I-LDL in a dose-dependent manner. The drug inhibited cholesterol synthesis and esterification without affecting cellular cholesterol content and bile acid synthesis; cholesterol efflux was slightly increased. These results show that the inhibition of cholesterol synthesis together with the enhanced expression of LDL receptors may partially explain the hypocholesterolemic activity of compound AR12456. |
| Effect of trifluoperazine on cholesterol metabolism of smooth muscle cells exposed to hypercholesterolemic medium in vitro Mehta, U. and D. Kaul (1990), Biochem Med Metab Biol 44(2): 151-8. Abstract: We recently demonstrated that the preventive effect of trifluoperazine (a potent inhibitor of calmodulin, protein kinase C, and phospholipase A2) on cholesterol-induced atherogenic activity of smooth muscle cells was mediated through its ability to inhibit smooth muscle cellular DNA synthesis coupled with stimulation of LDL receptor synthesis. The present study addressed the effect of trifluoperazine on cholesterol metabolism of aortic SMCs enriched with cholesterol through the nonreceptor pathway and revealed that (a) TFP caused inhibition of cholesterol synthesis compared with control cells bathed with hypercholesterolemic medium alone. (b) The drug also caused inhibition of free cholesterol and cholesteryl ester accumulation within smooth muscle cells compared to control cells. These results demonstrate that the preventive effect of TFP on atherogenic activity of smooth muscle cells may also be due to its ability to affect the altered/modified cholesterol metabolism of smooth muscle cells exposed to hypercholesterolemic medium in vitro. |
| Effect of truncated forms of the steroidogenic acute regulatory protein on intramitochondrial cholesterol transfer Wang, X., Z. Liu, et al. (1998), Endocrinology 139(9): 3903-12. Abstract: It has been proposed that the steroidogenic acute regulatory (StAR) protein controls hormone-stimulated steroid production by mediating cholesterol transfer to the mitochondrial inner membrane. This study was conducted to determine the effect of wild-type StAR and several modified forms of StAR on intramitochondrial cholesterol transfer. Forty-seven N-terminal or 28 C-terminal amino acids of the StAR protein were removed, and COS-1 cells were transfected with pCMV vector only, wild-type StAR, N-47, or the C-28 constructs. Lysates from the transfected COS-1 cells were then incubated with mitochondria from MA-10 mouse Leydig tumor cells that were preloaded with 3Hcholesterol. After incubation, mitochondria were collected and fractionated on sucrose gradients into outer membranes, inner membranes, and membrane contact sites, and 3Hcholesterol content was determined in each membrane fraction. Incubation of MA-10 mitochondria with wild-type StAR containing cell lysate resulted in a significant 34.9% increase in 3Hcholesterol content in contact sites and a significant 32.8% increase in inner mitochondrial membranes. Incubations with cell lysate containing N-47 StAR protein also resulted in a 16.4% increase in 3Hcholesterol in contact sites and a significant 26.1% increase in the inner membrane fraction. In contrast, incubation with the C-28 StAR protein had no effect on cholesterol transfer. The cholesterol-transferring activity of the N-47 truncation, in contrast to that of the C-28 mutant, was corroborated when COS-1 cells were cotransfected with F2 vector (containing cytochrome P450 side-chain cleavage enzyme, ferridoxin, and ferridoxin reductase) and either pCMV empty vector or the complementary DNAs of wild-type StAR, N-47 StAR, or C-28 StAR. Pregnenolone production was significantly increased in both wild-type and N-47-transfected cells, whereas that in C-28-transfected cells was similar to the control value. Finally, immunolocalization studies with confocal image and electron microscopy were performed to determine the cellular location of StAR and its truncated forms in transfected COS-1 cells. The results showed that wild-type and most of the C-28 StAR protein were imported into the mitochondria, whereas most of N-47 protein remained in the cytosol. These studies demonstrate a direct effect of StAR protein on cholesterol transfer to the inner mitochondrial membrane, that StAR need not enter the mitochondria to produce this transfer, and the importance of the C-terminus of StAR in this process. |
| Effect of two common polymorphisms in the ATP binding cassette transporter A1 gene on HDL-cholesterol concentration Woll, P. S., N. Q. Hanson, et al. (2005), Clin Chem 51(5): 907-9. |
| Effect of unesterified cholesterol on the activity of cholesteryl ester transfer protein Rajaram, O. V., R. Y. Chan, et al. (1994), Biochem J 304 (Pt 2): 423-30. Abstract: Cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from high-density lipoprotein to triacylglycerol-rich lipoproteins and the transfer of triacylglycerols in the reverse direction. The activity of CETP has been studied using a continuous fluorescence assay which measures the excimer fluorescence of cholesteryl 1-pyrene decanoate in a synthetic donor microemulsion as the indicator of cholesteryl ester transfer. Emulsions were composed of cholesteryl oleate and egg phosphatidylcholine and had an average particle size of 14 +/- 1 nm as calculated from the molar volume of the components. The effect of changing the physical state of the emulsion surface was examined by including unesterified cholesterol in the donor and acceptor particles. The rate of CETP-induced transfer of the fluorescent cholesteryl ester between microemulsion particles increased when unesterified cholesterol was present at concentrations up to 17 mol% relative to phospholipid. The presence of cholesterol also changed the exchange kinetics from an apparent single-exponential to a double-exponential phenomenon. Binding of CETP to the emulsion surface was accompanied by an enhancement of fluorescence which was used to measure the binding equilibria. The enhancement of exchange due to the presence of cholesterol did not correlate with any increased binding of CETP to the emulsion surface. The presence of unesterified cholesterol in the donor did not affect the rate of transfer of the fluorescent cholesteryl ester when unlabelled emulsion was replaced by high-density lipoprotein as the acceptor. The studies demonstrate the use of microemulsions of defined size and composition for the study of the mechanism of action of CETP. |
| Effect of unesterified cholesterol on the compartmentation of a fluorescent cholesteryl ester in a lipoprotein-like lipid microemulsion Li, Q. T. and W. H. Sawyer (1992), J Lipid Res 33(4): 503-12. Abstract: The access of enzymes and lipid transfer proteins to neutral lipids located predominantly in the core compartment of lipoproteins may be determined to some degree by the solubility of the neutral lipids in the surface monolayer of phospholipid. This report concerns the hypothesis that unesterfied cholesterol can affect the partition of a cholesteryl ester between the surface monolayer of a lipid emulsion and the internal core compartment, thus controlling the degree to which the cholesteryl ester is presented at the emulsion surface. For microemulsions composed of dimyristoyl phosphatidylcholine and cholesteryl oleate, the addition of unesterified cholesterol results in an increase in the particle size from about 170 nm diameter to 210 nm diameter at 13.5 mol% unesterified cholesterol. Fluorescent quenching methods were devised to determine the apparent partition of a fluorescent cholesteryl ester (cholesteryl anthracene-9-carboxylate) between surface and core compartments. The addition of unesterified cholesterol resulted in the movement of the fluorescent cholesteryl ester from the surface monolayer to the core compartment. The apparent partition coefficient, defined as the ratio of the concentration of probe in the monolayer to that in the core, decreased from 1.03 in the absence of unesterfied cholesterol to 0.54 at 28 mol% unesterified cholesterol in the emulsion. In this process, the fluorescent cholesteryl ester becomes less accessible to a quencher (5-doxyl stearate) located in the surface monolayer. The decrease in the surface curvature resulting from incorporation of unesterified cholesterol into the particle does not influence this quenching process. We conclude that the presence of unesterified cholesterol in the emulsion causes the fluorescent cholesteryl ester to become less soluble in the surface monolayer. |
| Effect of up-regulating individual steps in the reverse cholesterol transport pathway on reverse cholesterol transport in normolipidemic mice Alam, K., R. S. Meidell, et al. (2001), J Biol Chem 276(19): 15641-9. Abstract: Cholesterol acquired by extrahepatic tissues (from de novo synthesis or lipoproteins) is returned to the liver for excretion in a process called reverse cholesterol transport (RCT). We undertook studies to determine if RCT could be enhanced by up-regulating individual steps in the RCT pathway. Overexpression of 7alpha-hydroxylase, Scavenger receptor B1, lecithin:cholesterol acyltransferase (LCAT), or apoA-I in the liver did not stimulate cholesterol efflux from any extrahepatic tissue. In contrast, infusion of apoA-I.phospholipid complexes (rHDL) that resemble nascent HDL markedly stimulated cholesterol efflux from tissues into plasma. Cholesterol effluxed to rHDL was initially unesterified but by 24 h this cholesterol was largely esterified and had shifted to normal HDL (in mice lacking cholesteryl ester transfer protein) or to apoB containing lipoproteins (in cholesteryl ester transfer protein transgenic mice). Most of the cholesterol effluxed into plasma in response to rHDL came from the liver. However, an even greater proportion of effluxed cholesterol was cleared by the liver resulting in a transient increase in liver cholesterol concentrations. Fecal sterol excretion was not increased by rHDL. Thus, although rHDL stimulated cholesterol efflux from most tissues and increased net cholesterol movement from extrahepatic tissues to the liver, cholesterol flux through the entire RCT pathway was not increased. |
| Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans Woollett, L. A., D. D. Buckley, et al. (2003), J Lipid Res 44(5): 935-42. Abstract: Qualitative and quantitative changes in intraluminal bile acid composition may alter cholesterol absorption and synthesis and LDL receptor expression. In a randomized crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day ursodeoxycholic acid (UDCA) or no bile acid supplement (control) for 20 days while being fed a controlled diet (AHA Step II). A liquid meal of defined composition was then given and luminal samples collected. Cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods. With UDCA treatment, bile was enriched significantly (P < 0.0001) to 40.6 +/- 2.6% (mean +/- SEM) compared with 2.2 +/- 2.6% for controls. Regardless, plasma total, HDL, and LDL cholesterol were unchanged with UDCA treatment. Intraluminal cholesterol solubilized in the aqueous phase during the entire collection was decreased (P = 0.012) in UDCA-treated subjects (101.0 +/- 7.2 mg/ml/120 min) compared with controls (132.5 +/- 7.2 mg/ml/120 min.). Percent micellar cholesterol was increased in UDCA-treated versus controls after meal ingestion. No changes were found in cholesterol absorption, FSR, or LDL receptor mRNA with UDCA treatment compared with controls. Thus, despite marked enrichment in luminal bile with UDCA and decreased cholesterol solubilization, no differences in cholesterol absorption or metabolism are found when diet and genetic differences in absorption are carefully controlled. |
| Effect of ursodeoxycholic acid on hepatic cholesterol metabolism Einarsson, K. (1994), Scand J Gastroenterol Suppl 204: 19-23. Abstract: Oral administration of ursodeoxycholic acid (UDCA) renders bile unsaturated with cholesterol by reducing the hepatic output of cholesterol. Theoretically, several mechanisms may be of importance. In the present overview, the effect of treatment with UDCA on hepatic cholesterol metabolism is evaluated, in particular the influence on hepatic cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity, bile acid synthesis, 7 alpha-hydroxylation of cholesterol, and esterification of cholesterol--acyl coenzyme A: cholesterol acetyltransferase (ACAT) activity. It is apparent that UDCA treatment does not inhibit the hepatic HMG CoA reductase activity. Neither is ACAT activity or the cholesteryl ester content changed by UDCA. The catabolism of cholesterol to bile acids is unaffected or slightly increased during administration of UDCA. It is concluded that a stimulated degradation of cholesterol to bile acids may partly explain the decrease in hepatic secretion of cholesterol obtained during UDCA administration. It is suggested that the reduction in cholesterol absorption from the intestine seen during UDCA therapy may also be of importance. |
| Effect of vitamin C deficiency and excess on the liver: a histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet Sharma, P., J. Pramod, et al. (1990), Indian J Pathol Microbiol 33(4): 307-13. Abstract: When guinea pigs were kept on a restricted vitamin C intake of only 0.5 mg daily, their serum ascorbic acid fell to 0.16 +/- 0.06 mg/d1 in 16 weeks as compared to 0.73 +/- 0.11 in control. This was associated with significant increase in liver cholesterol and triglycerides. When they were simultaneously challenged with a high cholesterol load, this fat accumulation was markedly exaggerated. The weight of the liver now increased by almost two-and-half times. Liver cholesterol rose to 12.90 +/- 2.63 mg/gm as compared to 3.23 +/- 0.56 mg/gm with low vitamin C alone. Histopathology showed marked distension and vacuolation of hepatocytes, focal necrosis and fibroplasia. Administration of excess vitamin C (100 mg daily) significantly countered these changes. The vitamin C-lipid relationship has important clinical bearings and liver could be an important site of vitamin C action. |
| Effect of vitamin C depletion on serum cholesterol and lipoprotein levels in ODS (od/od) rats unable to synthesize ascorbic acid Uchida, K., Y. Nomura, et al. (1990), J Nutr 120(10): 1140-7. Abstract: The effect of ascorbic acid deficiency on serum and liver cholesterol, phospholipid and triglyceride levels, serum lipoprotein levels and serum lipoprotein cholesterol levels were examined in male rats with a hereditary defect in ascorbic acid synthesis (ODS rats). Male homozygotes (od/od) and male rats of their parent strain (+/+) were each divided into four treatment groups and were fed vitamin C-deficient or vitamin C-replete diets containing either 0 or 0.5% cholesterol. During the 3-wk feeding-period the ODS (od/od) rats fed the vitamin C-deficient diet gradually decreased food intake, resulting in a lower body weight than that of od/od rats given ascorbic acid. The serum cholesterol level was significantly higher in the vitamin C-deficient od/od rats fed the cholesterol diet, and it tended to be higher in those fed the control (0% cholesterol) diet, whereas the liver lipid levels remained unchanged relative to those in od/od rats fed the vitamin C-replete diet. The serum very low density lipoprotein and high density lipoprotein (HDL) cholesterol levels were lower in od/od rats fed the vitamin C-deficient diet without cholesterol, but intermediate density lipoprotein and low density lipoprotein cholesterol levels were markedly higher in the vitamin C-deficient od/od rats than in od/od rats given ascorbic acid, regardless of dietary cholesterol level. The ratio of HDL2 cholesterol to HDL3 cholesterol was also higher in the vitamin C-deficient od/od rats. The parent strain of the od/od rats (+/+) showed no change due to vitamin C deficiency. These results suggest that vitamin C deficiency delays low density lipoprotein metabolism and produces hypercholesterolemia in male od/od rats. |
| Effect of vitamin C supplementation on lipoprotein cholesterol, apolipoprotein, and triglyceride concentrations Jacques, P. F., S. I. Sulsky, et al. (1995), Ann Epidemiol 5(1): 52-9. Abstract: Plasma ascorbic acid (AA) frequently is positively correlated with high-density-lipoprotein (HDL) cholesterol and inversely related to total cholesterol concentration. To determine if vitamin C intake can alter cholesterol concentration, we examined the effect of vitamin C supplementation (1 g/d) on lipoprotein cholesterol and triglyceride levels in 138 subjects, aged 20 to 65 years, who completed an 8-month randomized, double-blinded, placebo-controlled trial. Individuals with higher levels of plasma AA (> 80 mumol/L for men and > 90 mumol/L for women), HDL cholesterol (> 1.4 mmol/L for men and > 1.7 mmol/L for women), and total cholesterol (> 6.7 mmol/L) were excluded from this trial. We observed no overall effect of supplementation on plasma concentrations of HDL, LDL, or total cholesterol, apolipoprotein (apo) B, or triglyceride. We did observe a marginally significant (P < 0.10) increase of 1.9 mumol/L (5.3 mg/dL) in apo A-I concentration with supplementation and a significant (P < 0.05) difference of 0.10 mmol/L (3.8 mg/dL) in HDL cholesterol concentration between vitamin C and placebo treatment in a nonrandomized subgroup of individuals (n = 43) and a baseline plasma AA level less than 55 mumol/L. Although the apo A-I concentration increase was only marginally significant with supplementation, change in plasma AA concentration was significantly (P < 0.05) correlated with change in apo A-I concentration in the entire sample. The overall results of this trial were negative, but our data do not allow us to rule out the possibility that vitamin C supplementation might increase HDL cholesterol or apo A-I concentrations among individuals with lower plasma AA levels. |
| Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits Ozer, N. K., O. Sirikci, et al. (1998), Free Radic Biol Med 24(2): 226-33. Abstract: The preventive effect of vitamin E and Probucol against atherosclerosis in rabbits were compared. Atherosclerosis was induced by a 2% cholesterol-containing vitamin E-poor diet (5-10 ppm). Six groups of five rabbits each were studied. Group I (control) was fed on a vitamin E-poor diet. The other groups had the following supplements: group II, 50 mg/kg vitamin E i.m.; group III, 2% cholesterol; group IV, 2% cholesterol plus 50 mg/kg vitamin E i.m., group V, 2% cholesterol plus 1% Probucol; group VI, 2% cholesterol + 1% Probucol plus 50 mg/kg vitamin E i.m. After 4 weeks, aortas were removed and analyzed by light and scanning electron microscopy for atherosclerotic lesions. Samples of the media were analyzed for protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by microscopic examination, their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol-induced atherosclerotic lesions and the induction of protein kinase C activity. Probucol was not effective in preventing either cholesterol-induced atherosclerotic lesions or the induction of protein kinase C activity. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as Probucol, and therefore, may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells ex vivo suggest an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis. |
| Effect of vitamin E on aortic lipid oxidation and intimal proliferation after arterial injury in cholesterol-fed rabbits Upston, J. M., P. K. Witting, et al. (2001), Free Radic Biol Med 31(10): 1245-53. Abstract: Oxidized low-density lipoproteins (LDL) are implicated in atherosclerosis. However, large-scale intervention studies designed to test whether antioxidants, such as vitamin E, can ameliorate cardiovascular disease have generated ambivalent results. This may relate to the fact that the mechanism whereby lipid oxidation is initiated in vivo is unknown and the lack of direct evidence for a deficiency of antioxidants in atherosclerotic lesions. Further, there is little evidence to suggest that vitamin E acts as an antioxidant for lipid peroxidation in vivo. Here we tested the antioxidant effect of dietary vitamin E (alpha-tocopherol) supplementation on intimal proliferation and lipid oxidation in balloon-injured, hypercholesterolemic rabbits. alpha-Tocopherol supplementation increased vascular content of alpha-tocopherol over 30-fold compared to nonsupplemented and alpha-tocopherol-deficient chows. Balloon injury resulted in oxidized lipid deposition in the aorta. Maximum levels of primary lipid oxidation products, measured as hydroperoxides of esterified lipid (LOOH) and oxidized linoleate (HODE), were 0.22 and 1.10 nmol/mg, representing 0.21 and 0.39% of the precursor molecule, respectively. Secondary lipid oxidation products, measured as oxysterols, were maximal at 5.60 nmol/mg or 1.48% of the precursor compound. Vascular HODE and oxysterols were significantly reduced by vitamin E supplementation. However, the intima/media ratio of aortic vessels increased with vitamin E supplementation, suggesting that the antioxidant promoted intimal proliferation. Thus, the study demonstrates a dissociation of aortic lipid oxidation and lesion development, and suggests that vitamin E does not prevent lesion development in this animal model. |
| Effect of vitamin E on vascular integrity in cholesterol-fed guinea pigs Qiao, Y., M. Yokoyama, et al. (1993), Arterioscler Thromb 13(12): 1885-92. Abstract: This study was designed to clarify the effects of vitamin E on the alterations in proteoglycan distribution and vascular permeability, which were examined by immunohistochemical and ultrastructural techniques in the aortas of cholesterol-fed guinea pigs. The animals were divided into three groups: a control group, a cholesterol group, and a vitamin E group. Serum levels of cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, and thiobarbituric acid-reactive substances were measured. An increase in thiobarbituric acid-reactive substances was observed in the cholesterol group compared with control and vitamin E groups. Intimal atheromatous lesions of the aorta were significantly decreased in the vitamin E group compared with the cholesterol group. Histochemically, an increased distribution of proteoglycans such as chondroitin, dermatan, and heparan sulfates and ruthenium red reaction products in the intima; decreased glycocalyx on the endothelial surface; and increased permeability to horseradish peroxidase were revealed in the cholesterol group compared with the vitamin E group. Hypercholesterolemia, resulting in superoxide production, may have contributed to the endothelial damage and increased permeability to plasma proteins and lipids in the vascular wall of the cholesterol group. However, vitamin E administration inhibited lipid deposition and development of this abnormal permeability associated with an irregular distribution of proteoglycan. These results suggest that vitamin E preserves the morphological and functional integrity of the vascular wall and may contribute to the inhibition of atherogenesis in cholesterol-fed guinea pigs. |