| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Increased A beta peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease Roher, A. E., N. Weiss, et al. (2002), Biochemistry 41(37): 11080-90. Abstract: Relative to the gray matter, there is a paucity of information regarding white matter biochemical alterations and their contribution to Alzheimer's disease (AD). Biochemical analyses of AD white matter combining size-exclusion, normal phase, and gas chromatography, immunoassays, and Western blotting revealed increased quantities of Abeta40 and Abeta42 in AD white matter accompanied by significant decreases in the amounts of myelin basic protein, myelin proteolipid protein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase. In addition, the AD white matter cholesterol levels were significantly decreased while total fatty acid content was increased. In some instances, these white matter biochemical alterations were correlated with patient apolipoprotein E genotype, Braak stage, and gender. Our observations suggest that extensive white matter axonal demyelination underlies Alzheimer's pathology, resulting in loss of capacitance and serious disturbances in nerve conduction, severely damaging brain function. These white matter alterations undoubtedly contribute to AD pathogenesis and may represent the combined effects of neuronal degeneration, microgliosis, oligodendrocyte injury, microcirculatory disease, and interstitial fluid stasis. To accurately assess the success of future therapeutic interventions, it is necessary to have a complete appreciation of the full scope and extent of AD pathology. |
| Increased activity of lecithin:cholesterol acyltransferase during short-term oral estrogen progestin replacement therapy in a group of postmenopausal women Ulloa, N., C. Verdugo, et al. (1998), Metabolism 47(3): 297-300. Abstract: The aim of the study was to assess the short-term effect of estrogen-progestin therapy on the plasma level of lecithin: cholesterol acyltransferase (LCAT EC 2.3.1.43), a key enzyme in the cholesterol reverse-transport process. The trial included 21 women with at least 6 months of menopause, which was confirmed by anamnesis, physical evaluation, and follicle-stimulating hormone (FSH) determination. Women receiving pharmacological treatment or who had any kind of endocrine disorder were excluded. In addition, we evaluated and confirmed normal Papanicolaou and mammography tests in all 21 women included in the trial. They received conjugated equine estrogen 0.625 mg daily, plus cyclic medroxyprogesterone acetate (5 mg daily) for 12 days each month. Plasma levels of LCAT, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apoB, and apoAI were evaluated before and after 1 and 3 months of therapy. Pretherapy and posttherapy results were analyzed statistically by Wilcoxon's rank-sum test for paired samples. No significant changes were observed either for body mass index or for blood pressure. A significant increase in plasma LCAT activity was found at the first and third month posttherapy (P <.005). In addition, after 3 months of therapy, HDL-C significantly increased (P <.005), in contrast to the significant decrease detected in total cholesterol (P <.025), LDL-C (P <.005), cholesterol to HDL-C and LDL-C/HDL-C ratios (P <.005). Triglyceride levels did not show significant modification. In conclusion, our results indicate that short-term estrogen-progestin therapy produces a significant increase in plasma LCAT activity, as well as beneficial changes in the lipid profile, in postmenopausal women. |
| Increased acylCoA-cholesterol ester acyltransferase activity in gallbladder mucosa in patients with gallbladder cholesterolosis Watanabe, F., H. Hanai, et al. (1998), Am J Gastroenterol 93(9): 1518-23. Abstract: OBJECTIVE: Although cholesterolosis of the human gallbladder is a relatively common disease, its etiology has not been fully understood. The aim of this study was to determine this etiology. METHODS: The lipid composition of the gallbladder mucosa and gallbladder bile and the enzyme activities (acylCoA-cholesterol ester acyltransferase ACAT and cholesterol ester hydrolase CEH) of the gallbladder mucosa were measured in control subjects, patients with cholesterolosis, and patients with cholesterol gallstone disease. RESULTS: Levels of cholesterol ester in gallbladder mucosa in patients with cholesterolosis (n = 12) were higher than those in control subjects (n = 8). With regard to the lipid content in gallbladder bile, no differences were found in concentrations of cholesterol, phospholipids, and bile acids among control subjects (n = 11), patients with cholesterolosis (n = 13), and those with cholesterol gallstone disease (n = 15). In gallbladder mucosa, ACAT activity was significantly higher in patients with cholesterolosis (n = 10) than in control subjects (n = 8), whereas CEH activity did not differ between the two groups. As a result, the ACAT/CEH activity ratio was higher in patients with cholesterolosis than in control subjects. CONCLUSIONS: It would be suggested that cholesterol ester synthesis of gallbladder mucosa might play an etiological role in the development of cholesterolosis. |
| Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia Brinton, E. A., S. Eisenberg, et al. (1991), J Clin Invest 87(2): 536-44. Abstract: Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility. |
| Increased beef consumption increases apolipoprotein A-I but not serum cholesterol of mildly hypercholesterolemic men with different levels of habitual beef intake Smith, D. R., R. Wood, et al. (2002), Exp Biol Med (Maywood) 227(4): 266-75. Abstract: The objective of this research was to compare the effects of a lean beef enriched in oleic acid to a beef that is typical of the commercial beef consumed in the United States. Ten mildly hypercholesterolemic men, ages 34-58 years old, were selected from the Texas A&M University faculty and staff. Subjects were randomly assigned to one of two diets for a 6-week duration followed by a crossover after a 4-week habitual diet washout period. Diets were consumed daily for a 6-week study period. Participants substituted lean beef obtained from Wagyu bullocks or commercial beef for the meat typically consumed. Total cholesterol, apolipoproteins A-I and B, triacylglycerols, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were measured in serum samples collected weekly. Beef type had no effect on any measured variable. There were no significant differences between baseline HDL or LDL cholesterol concentrations after the consumption of the beef test diets. Apolipoprotein A-I, serum glucose, and uric acid concentrations were elevated by the additional dietary beef. Analysis of records of customary diets indicated that one group consumed 160 g of beef daily, whereas the other group consumed only 26 g of beef daily. Therefore, post hoc analyses tested the habitual beef intake x treatment time interaction. LDL cholesterol concentration was markedly higher in the group with low habitual beef intake (180 vs 144 mg/dl), and HDL cholesterol was slightly higher (44 vs 40 mg/dl; post-test values) than for the group with high habitual beef intake, but there were no habitual intake x time interactions for LDL or HDL cholesterol. Creatinine and blood urea nitrogen concentrations also were greater in the individuals habitually consuming less beef. This study had three important findings: i) a lean beef source enriched with oleic acid was no different from commercial beef in its effect on lipoprotein fractions; ii) neither previous level of beef intake nor baseline LDL cholesterol concentration influenced the serum cholesterol response to added dietary beef, which was negative; and iii) apolipoprotein A-I, but not HDL or LDL cholesterol, was sensitive to the additional dietary beef. |
| Increased bile acid concentration in liver tissue with cholesterol gallstone disease Honda, A., T. Yoshida, et al. (1995), J Gastroenterol 30(1): 61-6. Abstract: Patients with cholesterol gallstone disease have a reduced pool of bile acids. Overly sensitive feedback inhibition of bile acid synthesis has been postulated to explain this size reduction. To test this hypothesis, hepatic bile acid concentration and the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for bile acid biosynthesis, were determined in ten patients with cholesterol gallstones and ten patients without gallstones. The bile acids present in liver tissue are the sum of those returning to liver and those newly synthesized in liver. If an overly sensitive feedback inhibition truly existed in our gallstone patients, a decreased concentration of hepatic bile acids would have been expected. However, patients with cholesterol gallstones had significantly higher total (143.3 +/- 25.5 vs 64.5 +/- 10.8 nmol/g liver, P < 0.01), chenodeoxycholic (64.1 +/- 9.9 vs 29.8 +/- 5.4, P < 0.01), deoxycholic (22.8 +/- 10.9 vs 2.0 +/- 0.7, P < 0.05), and ursodeoxycholic acid (6.2 +/- 1.4 vs 1.5 +/- 0.6, P < 0.01) concentrations than patients without gallstones. The activity of cholesterol 7 alpha-hydroxylase did not differ significantly between the two groups. Impaired hepatic transport or secretion of bile acids is strongly suspected in cholesterol gallstone patients. The findings of the present study showed no evidence of overly sensitive feedback inhibition of bile acid synthesis in cholesterol gallstone patients. Bile acid pool size may be affected by the inappropriate increase of hepatic bile acids rather than by overly sensitive feedback inhibition. |
| Increased bile acid excretion and reduction of serum cholesterol after crenotherapy with salt-rich mineral water Capurso, A., V. Solfrizzi, et al. (1999), Aging (Milano) 11(4): 273-6. Abstract: The effect of a spring mineral water from Montecatini (Italy) on bile acid excretion, and lipid and apolipoprotein serum levels was evaluated. The study was conducted in subjects with serum total cholesterol (TC) level > 240 mg/dL and LDL cholesterol (LDL-C) > 170 mg/dL, over a 9-week period, with 3 weeks of dietary stabilization, 3 weeks of active treatment, and 3 weeks of tap-water treatment as a control period. Serum lipids and apolipoproteins, total and fractionated bile acid excretion, gallbladder motility, and safety parameters were evaluated. Active treatment with mineral water significantly reduced serum TC by 7.5%, LDL-C by 12.5%, TC/HDL-cholesterol ratio by 6.3%, and apolipoprotein B by 6.3%; total fecal bile acid excretion was increased by 98.9%, and gallbladder volume was reduced by 40%. The reduction in serum and LDL-cholesterol levels observed during the active treatment period ran parallel to the increased excretion of bile acids in the stools. We suggest that salt-rich spring water treatment reduces serum and LDL-cholesterol levels in subjects with mild hypercholesterolemia through a mechanism of increased excretion of fecal bile acid sterols. |
| Increased bile acid pool inhibits cholesterol 7 alpha-hydroxylase in cholesterol-fed rabbits Xu, G., G. Salen, et al. (1997), Gastroenterology 113(6): 1958-65. Abstract: BACKGROUND & AIMS: Cholesterol feeding unexpectedly inhibits cholesterol 7 alpha-hydroxylase in rabbits. The aim of this study was to explore the mechanism. METHODS: Twenty male New Zealand white rabbits were fed regular chow with and without 2% cholesterol for 10 days followed by 7 days of bile drainage. The activities of hepatic cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase that control bile acid synthesis in classic and alternative pathways were related to the size and composition of bile acid pool. RESULTS: After feeding cholesterol, plasma and hepatic cholesterol concentrations increased, the bile acid pool doubled (from 254 +/- 44 to 533 +/- 51 mg; P < 0.001), cholesterol 7 alpha-hydroxylase activity decreased 68% (P < 0.01), but sterol 27-hydroxylase activity increased 66% (P < 0.05) with increased cholic acid synthesis (P < 0.01). Bile drainage in the cholesterol-fed rabbits depleted the bile acid pool and stimulated down-regulated cholesterol 7 alpha-hydroxylase activity 11.4-fold (P < 0.001), although hepatic cholesterol remained elevated. Hepatic sterol 27-hydroxylase activity was unaffected. CONCLUSIONS: Feeding cholesterol increased hepatic cholesterol and stimulated sterol 27-hydroxylase and alternative bile acid synthesis, which expanded the bile acid pool and inhibited cholesterol 7 alpha-hydroxylase in rabbits. In distinction, hepatic sterol 27-hydroxylase was insensitive to changes in the bile acid pool. |
| Increased calcium intake reduces plasma cholesterol and improves vasorelaxation in experimental renal failure Jolma, P., P. Koobi, et al. (2003), Am J Physiol Heart Circ Physiol 285(5): H1882-9. Abstract: Chronic renal failure (CRF) is associated with abnormal lipid metabolism and high prevalence of vascular complications. Calcium salts are commonly used in CRF as phosphate binders. Increased calcium intake may also lower plasma cholesterol and beneficially influence vascular tone. Therefore, we investigated the influence of increasing dietary calcium from 0.3% to 3.0% for 8 wk after 5/6 nephrectomy (NTX) on plasma cholesterol and mesenteric resistance vessel tone in male Sprague-Dawley rats. The groups were Sham, Sham-Calcium, NTX, and NTX-Calcium (n = 10-11). Blood pressure was modestly elevated after NTX, whereas the plasma creatinine, urea nitrogen, phosphate, and parathyroid hormone levels were clearly increased. The high-calcium diet suppressed plasma phosphate and parathyroid hormone but was without effect on blood pressure. The NTX resulted in 1.6-fold elevation in plasma total cholesterol and 40% reduction in high density-to-low density lipoprotein ratio (HDL/LDL). However, the lipid profile in NTX rats on the high-calcium diet did not differ from sham-operated controls. The endothelium-mediated relaxations induced by acetylcholine were impaired in NTX rats, whereas the response was normalized by a high-calcium diet. No differences in vasorelaxations by the endothelium-independent vasodilator nitroprusside were detected. In conclusion, improved vasorelaxation after a high-calcium diet could be due to reduced plasma total cholesterol and ameliorated HDL/LDL ratio, although decreased plasma phosphate and parathyroid hormone may also play a significant role in the vascular effects of increased calcium intake. |
| Increased cellular cholesterol efflux in glycogen storage disease type Ia mice: a potential mechanism that protects against premature atherosclerosis Nguyen, A. D., C. J. Pan, et al. (2005), FEBS Lett 579(21): 4713-8. Abstract: Glycogen storage disease type Ia (GSD-Ia) patients manifest a pro-atherogenic lipid profile but are not at elevated risk for developing atherosclerosis. Serum phospholipid, which correlates positively with the scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux, and apolipoprotein A-IV and E, acceptors for ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol transport, are increased in GSD-Ia mice. Importantly, sera from GSD-Ia mice are more efficient than sera from control littermates in promoting SR-BI- and ABCA1-mediated cholesterol effluxes. As the first step in reverse cholesterol transport, essential for cholesterol homeostasis, these observations provide one explanation why GSD-Ia patients are apparently protected against premature atherosclerosis. |
| Increased cellular cholesterol upregulates high density lipoprotein binding to rat luteal cells Ferreri, K., F. Talavera, et al. (1992), Endocrinology 131(5): 2059-64. Abstract: Rat luteal cells preferentially utilize cholesterol derived from high density lipoproteins (HDL) as a substrate for steroid hormone synthesis. The uptake of cholesterol from HDL by these cells is in contrast to nonsteroidogenic cells, which export cholesterol to HDL. A previous study demonstrated that HDL binding to luteal cell membranes was increased in conjunction with in vivo cholesterol depletion or cholesterol loading of the ovary induced by pharmacological agents. These results suggest a biphasic regulation of the HDL receptor in luteinized rat ovaries. In the present studies, the in vitro regulation of HDL binding in rat luteal cells by increased intracellular cholesterol was examined. Cultured luteal cells were incubated with increasing doses of low density lipoproteins (LDL) for 2 days after which the cellular sterol content and the effects on progesterone production and HDL binding were measured. As expected, the LDL treatment increased total cellular sterol content in a dose-dependent manner, resulting in a 2.1-fold increase over control at a dose of 1 mg LDL/ml. Increased cellular cholesterol was accompanied by a comparable increase in progesterone secretion. These results suggest that exogenous cholesterol was utilized by these cells. The LDL treatment also increased the binding of HDL to the cells in a dose-dependent manner to a maximum of 2.2-fold over control. The effect of increased cellular sterol on HDL binding was also examined using a more polar cholesterol derivative, 25-hydroxycholesterol. Cells were cultured for 2 days in media containing 0.3-40 micrograms/ml 25-hydroxycholesterol in the presence of 100 micrograms/ml aminoglutethimide, an inhibitor of cholesterol metabolism. The HDL binding to luteal cells exhibited dose-dependent up-regulation by 25-hydroxycholesterol with a 5.8-fold increase in binding at the maximum dose tested. Equilibrium binding studies using cells treated with 10 micrograms/ml 25-hydroxycholesterol revealed a 2.1-fold increase in the number of HDL binding sites on the luteal cells without affecting the binding affinity. From the results of this study, it is concluded that HDL binding in rat luteal cells is up-regulated by an increase in the intracellular cholesterol level. |
| Increased cholesterol absorption by hyperlipidemia atherosclerosis prone (LAP) Japanese quail Iwasaki, H., H. Oku, et al. (2000), J Nutr Sci Vitaminol (Tokyo) 46(5): 235-9. Abstract: The present study describes the cholesterol absorption by hyperlipidemia atherosclerosis prone (LAP) Japanese quail to address their high susceptibility to experimental atherosclerosis. The apparent cholesterol absorption rate of LAP quail was compared with that of commercially available (CA) Japanese quail. After 14 d of cholesterol feeding by gavage, it was found that the cholesterol excretion of LAP quail was significantly lower than that of CA quail. The fecal excretion of bile acid and fat showed a similar tendency to that as shown with the case of cholesterol. The cholesterol feeding only increased the serum cholesterol level of LAP quail, and this trend holds true for the liver lipid concentration. The expression level of liver cholesterol 7alpha-hydroxylase mRNA showed no difference between LAP and CA strains under the conditions of cholesterol loading. These results showed that the cholesterol absorption by LAP quail is significantly higher than that by CA quail, which may reasonably explain the higher susceptibility of this strain to experimental atherosclerosis. |
| Increased cholesterol content in erythrocyte membranes of patients with chronic renal failure treated with hemodialysis Jendryczko, A., W. Grzeszczak, et al. (1995), Pol Arch Med Wewn 93(3): 203-7. Abstract: The investigate whether the blood rheological disturbances occurring in hemodialyzed patients are related to the erythrocyte lipid composition, cholesterol and phospholipid content was studied of the erythrocyte membrane. The study included 40 patients with chronic renal insufficiency. 34 of them had hypertension and proteinuria. The cholesterol/phospholipid ratio was significantly higher in the patients after hemodialysis (mean 2.48; SD 0.14) compared with the patients before hemodialysis (mean 2.08; SD 0.19). There was a significant increase of cholesterol in subgroup with hypertension and proteinuria. A significant correlation was found between membrane cholesterol/phospholipid ratio and serum levels of LDL-cholesterol. |
| Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium Smith, R. D., E. B. Babiychuk, et al. (2005), Am J Physiol Cell Physiol 288(5): C982-8. Abstract: Uterine quiescence is essential for successful pregnancy. Cholesterol and triglycerides are markedly increased in pregnancy. Cholesterol is enriched in microdomains of the plasma membrane known as rafts and caveolae. Both lipid rafts and caveolae have been implicated in cellular signaling cascades. The purpose of this work was to investigate whether manipulation of cholesterol content alters uterine contractility. Late pregnancy (19-21 days) rats were humanely euthanized and strips of longitudinal myometrium were then dissected. Force and Ca(2+) measurements were simultaneously recorded and cholesterol increased by the addition of 5 mg/ml cholesterol or 0.25 mg/ml low-density lipoproteins (LDLs) or reduced by 2% methyl-beta-cyclodextrin (MCD) or 2 U/ml cholesterol oxidase addition to the perfusate. Both LDLs and cholesterol profoundly inhibited spontaneous uterine force production and associated Ca(2+) transients; frequency, amplitude, and duration of contraction were all significantly reduced compared with preceding control contractions. Force and Ca(2+) were also reduced by cholesterol when 1 nM oxytocin was used to stimulate the myometrium. Uterine activity was significantly increased by cholesterol extraction with MCD or cholesterol oxidase treatment. Electron microscopy confirmed the lipid raft disrupting effect of MCD, as formerly electron microscopy-visible caveolae in the myometrial cell membrane all but disappeared after MCD treatment. These data show that uterine smooth muscle cell cholesterol content is critically important for functional activity. A novel finding of our study is that cholesterol is inhibitory for force generation. It may be one of the mechanisms operating to maintain uterine quiescence throughout gestation and may also contribute to difficulties in labor suffered by obese women. |
| Increased cholesterol efflux in apolipoprotein AI (ApoAI)-producing macrophages as a mechanism for reduced atherosclerosis in ApoAI((-/-)) mice Major, A. S., D. E. Dove, et al. (2001), Arterioscler Thromb Vasc Biol 21(11): 1790-5. Abstract: The concentration of apolipoprotein (apo) AI in the artery wall is thought to enhance cellular cholesterol efflux and protect against atherosclerosis. It has been shown that although macrophages do not make apoAI, they respond to it by increased cholesterol efflux. We hypothesized that macrophage production of apoAI would increase cholesterol efflux and reduce atherogenesis. In this study, we produced mice expressing human apoAI under the control of the macrophage-specific scavenger receptor-A promoter (mphi-AI). Human apoAI was detectable in the serum HDL fraction of mphi-AI transgenic mice at concentrations too low to affect serum cholesterol or HDL levels. Immunoblotting showed the presence of human apoAI in transgenic macrophage culture supernatants, mostly as lipoprotein-free protein, with a small component associated with HDL-like particles. Atherosclerosis studies using apoAI((-/-)) mice transplanted with mphi-AI bone marrow showed that in the absence of macrophage-derived apoE, local expression of apoAI reduced diet-induced lesions in the proximal aorta. Additionally, mphi-AI macrophages showed a 40% increase in cholesterol efflux compared with control macrophages. These data support the hypothesis that apoAI production by macrophages in the artery wall is protective against atherosclerosis. This protection is likely mediated by increased cholesterol efflux and decreased foam cell formation in vivo. |
| Increased cholesterol efflux potential of sera from ApoA-IMilano carriers and transgenic mice Franceschini, G., L. Calabresi, et al. (1999), Arterioscler Thromb Vasc Biol 19(5): 1257-62. Abstract: The ability of HDL to remove cholesterol from peripheral cells and drive it to the liver for excretion is believed to explain most of the strong inverse correlation between plasma HDL cholesterol levels and coronary heart disease. Carriers of the ApoA-IMilano (A-IM) mutant have a severe hypoalphalipoproteinemia but are not at increased risk for premature of coronary heart disease. To explain this apparent paradox, we compared the capacity of serum from A-IM and control subjects to extract cholesterol from Fu5AH cells. Because the A-IM carriers are all heterozygotes for the mutation, we also compared the cholesterol efflux capacity of serum from transgenic mice expressing A-IM or wild-type ApoA-I (A-IWT), in the absence of murine ApoA-I. In the whole series of human or mouse sera, cholesterol efflux was significantly correlated with several HDL-related parameters; after adjustment for concomitant variables, the only parameter that remained significantly correlated with cholesterol efflux was the serum ApoA-I concentration (r2=0.85 in humans and 0.84 in mice). The same was true when samples from control subjects, A-IM carriers, A-IWT or A-IM mice were analyzed separately. Cholesterol efflux to sera from the A-IM carriers was only reduced slightly compared with control sera (25.0+/-4.2% versus 30.4+/-3.3%), although there was a large reduction (-45%) in the serum ApoA-I concentration in the former. Cholesterol efflux was also lower to sera from A-IM than A-IWT mice (15.6+/-3.8% versus 30. 1+/-7.1%), but less than expected from the 70% reduction in serum ApoA-I concentration. A relative efflux potential of serum was calculated in each group as the slope of the regression line fitting cholesterol efflux to ApoA-I concentrations. Therefore, the relative efflux potential reflects the relative efficiency of ApoA-I in determining cell cholesterol efflux. The relative efflux potential of mouse and human sera was in the following order: A-IM mice>A-IM carriers>A-IWT mice=control subjects, suggesting a gene-dosage effect of the A-IM mutation on the efficiency of serum to extract cholesterol from cells. The high efficiency of A-IM-containing HDL for cell cholesterol uptake would result in an improved reverse cholesterol transport in the A-IM carriers, possibly explaining the low susceptibility to atherosclerosis development. |
| Increased cholesterol esterase level by cholesterol loading of rat pancreatoma cells Huang, Y. and D. Y. Hui (1994), Biochim Biophys Acta 1214(3): 317-22. Abstract: This study used the rat pancreatoma AR42J cells as a model to determine the effects of cholesterol on cholesterol esterase biosynthesis. Incubation of AR42J cells with low-density lipoproteins (LDL) or with the cholesterol-induced beta-very-low-density lipoproteins did not result in changes in cellular cholesterol levels. These cholesterol-rich lipoproteins also had no effect on cholesterol esterase biosynthesis by the AR42J cells. Cellular cholesterol level was found to increase by approx. 2-fold after incubating the AR42J cells with cationized-LDL. The increase in cellular cholesterol level resulted in a higher level of cholesterol esterase secreted into the culture medium. The increased cellular cholesterol also resulted in higher amounts of cholesterol esterase detected in the AR42J cell lysate. The increase in cholesterol esterase level corresponded to a cholesterol-induced increase in steady-state level of cholesterol esterase mRNA. The results of this study, and our previous observation of post-transcriptional activation of cholesterol esterase induced by intestinal hormones (Huang, Y. and Hui, D.Y. (1991) J. Biol. Chem. 266, 6720-6725), suggested that cholesterol esterase biosynthesis may be regulated by transcriptional and translational mechanisms in response to hormonal and nutrient stimulation of the pancreatic acinar cells. Additionally, the regulation of cholesterol esterase biosynthesis by cholesterol loading of the pancreatic cells suggested a possible role of this enzyme in cholesterol metabolism. |
| Increased cholesterol in red cell membranes in women with pregnancy induced hypertension Jendryczko, A. and J. Tomala (1996), Ginekol Pol 67(2): 65-9. Abstract: The group of 24 women in the course of the first pregnancy complicated by hypertension was investigated. The higher amount of cholesterol in red cells membrane was found comparing to healthy pregnant and nonpregnant women. Cholesterol amount in red cells membranes is related to LDL cholesterolemia. |
| Increased cholesterol levels during paroxetine administration in healthy men Lara, N., G. B. Baker, et al. (2003), J Clin Psychiatry 64(12): 1455-9. Abstract: BACKGROUND: Despite the frequent use of selective serotonin reuptake inhibitors in patients with coronary heart disease (CHD), their effects on plasma lipid levels have not been systematically investigated. Our objective was to assess the effects of 8 weeks of paroxetine administration on plasma cholesterol and triglyceride levels. METHOD: Blood samples were collected at baseline, after 8 weeks of paroxetine administration, and post-discontinuation in 18 healthy male volunteers. RESULTS: In the 16 of 18 patients whose plasma levels of paroxetine indicated an unequivocal compliance to treatment, paroxetine administration induced an 11.5% increase in low-density lipoprotein cholesterol (LDL-C), which normalized after paroxetine discontinuation. CONCLUSION: The magnitude of the paroxetine-induced increase in LDL-C would lead to a minor increase in CHD risk in a minority of healthy male volunteers without associated CHD risk factors but might increase LDL-C sufficiently to warrant therapeutic intervention in patients with established CHD, based on the National Cholesterol Education Program guidelines. |
| Increased cholesterol synthesis in Chinese hamster ovary cells deficient in peroxisomes van Heusden, G. P., J. R. van Beckhoven, et al. (1992), Biochim Biophys Acta 1126(1): 81-7. Abstract: In a previous study we have shown that Chinese hamster ovary (CHO) cells deficient in intact peroxisomes, lack the nonspecific lipid transfer protein (nsL-TP; sterol carrier protein 2) (van Heusden, G.P.H., Bos, K., Raetz, C.R.H. and Wirtz, K.W.A. (1990) J. Biol. Chem. 265, 4105-4110). The consequences of the absence of peroxisomes and of nsL-TP on intracellular cholesterol metabolism have been investigated in two peroxisome-deficient CHO cell lines (CHO-82 and CHO-78). Compared with wild-type cells (CHO-K1), the incorporation of 3Hacetate into cholesterol was 3-fold higher in the CHO-82 cells and 2-fold higher in the CHO-78 cells. In agreement with an increased synthesis of cholesterol, a 2-3-fold higher 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was measured in both mutant cell lines. On the other hand, addition of low density lipoprotein (LDL), mevalonate (30 mM) or 25-hydroxycholesterol (2 micrograms/ml) to cells grown in lipoprotein-deficient serum, demonstrated that in both mutant cell lines the down-regulation of HMG-CoA reductase and of cholesterol synthesis were comparable to that in wild-type cells. These results strongly suggest that, in addition to down-regulation by LDL-derived cholesterol, mevalonate and 25-hydroxycholesterol, HMG-CoA reductase activity is under control of peroxisomes and/or nsL-TP. |