| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Estimation of serum apolipoprotein B by a modified homogeneous assay for HDL-cholesterol Sampson, M. L., G. Csako, et al. (2000), Clin Chem 46(6 Pt 1): 869-71. |
| Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits Haarbo, J., P. Leth-Espensen, et al. (1991), J Clin Invest 87(4): 1274-9. Abstract: Cardiovascular disease is currently the leading cause of death among women in the United States. To investigate the effect of postmenopausal hormone therapy on atherogenesis, we studied 75 cholesterol-fed female rabbits for 19 wk. The rabbits were randomly assigned to five groups. Four groups underwent bilateral ovariectomy followed by treatment with either 17 beta-estradiol, 17 beta-estradiol plus norethisterone acetate, 17 beta-estradiol plus levonorgestrel, or placebo. The fifth group had a sham operation and received placebo. The hormone groups had only one-third of the aortic accumulation of cholesterol found in the placebo groups, a difference that was highly statistically significant (P less than 0.0001). No significant differences in aortic accumulation of cholesterol were found in the hormone groups. This indicates that estrogen attenuates atherogenesis in cholesterol-fed ovariectomized rabbits and that two commonly prescribed progestogens do not counteract the effect. The beneficial effect of estradiol could only partly be explained by its lowering effects on serum total cholesterol or VLDL cholesterol, which implies that estradiol possesses additional beneficial effects, possibly a direct action on the arterial wall. |
| Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol-induced murine cholesterol gallstones Wang, H. H., N. H. Afdhal, et al. (2004), Gastroenterology 127(1): 239-49. Abstract: BACKGROUND & AIMS: Cholesterol gallstones are more common in women than men, and exposure to oral contraceptive steroids and conjugated estrogens increases the risk for gallstones. It is hypothesized that estrogen enhances cholesterol cholelithogenesis by augmenting functions of hepatic estrogen receptors (ERs). METHODS: To investigate molecular mechanisms of how estrogen influences cholesterol gallstones, we studied gonadectomized AKR/J mice of both genders that were implanted subcutaneously with pellets releasing 17beta-estradiol at 0, 3, or 6 microg/day and that were fed a lithogenic diet for 12 weeks. To test the hypothesis that ERs play a pivotal role in mediating lithogenic actions of estrogen and to dissect the potential pathophysiologic roles of each receptor subtype, ERalpha and ERbeta, in the formation of gallstones, we investigated gonadectomized mice treated with synthetic ER subtype-selective agonists or antagonists. RESULTS: 17beta-estradiol promoted gallstone formation by up-regulating hepatic expression of ERalpha but not ERbeta, and the lithogenic actions of estrogen can be blocked completely by the antiestrogenic ICI 182,780. The ERalpha-selective agonist propylpyrazole, but not the ERbeta-selective agonist diarylpropionitrile, augmented hepatic cholesterol output that resulted in cholesterol supersaturated bile and gallstones. Similar to the 17beta-estradiol treatment, tamoxifen significantly increased biliary cholesterol secretion and gallstone prevalence in both gonadectomized females and males. CONCLUSIONS: The hepatic ERalpha, but not ERbeta, plays a critical role in 17beta-estradiol-induced cholesterol gallstones. Our findings may offer a new approach to treat gallstones by inhibiting hepatic ER activity with a liver-specific, ERalpha-selective antagonist. |
| Estrogen stimulation of P450 cholesterol side-chain cleavage activity in cultures of human placental syncytiotrophoblasts Babischkin, J. S., R. W. Grimes, et al. (1997), Biol Reprod 56(1): 272-8. Abstract: The present study determined whether estrogen has a role in regulating the P450 cholesterol side-chain cleavage enzyme (P450scc) and/or de novo/deesterification cholesterol pathways involved in progesterone biosynthesis within human syncytiotrophoblasts. Human placental syncytiotrophoblasts were cultured for 48 h with estradiol, and P450scc activity was determined by the formation of progesterone from 25-hydroxycholesterol. Estradiol at 10(-7) or 10(-6) M and 25-hydroxycholesterol increased mean (+/- SE) progesterone production by syncytiotrophoblasts (ng/0.5 x 10(6) cells) to a value (19.2 +/- 1.1) that was 104% (p < 0.001) higher than that of the untreated controls (9.4 +/- 0.8) and 52% higher (p < 0.001) than with 25-hydroxycholesterol alone (12.6 +/- 0.9). The stimulation of progesterone secretion apparently was not the result of a change in progesterone metabolism to its principal metabolite, because 20alpha-hydroxypregn-4-en-3-one represented a minor secretory component (0.7-1.7 ng/0.5 x 10(6) cells) under these conditions, and levels were not substantially altered by estrogen. In contrast to the stimulatory effect of estradiol on P450scc activity, estrogen did not alter either the P450scc mRNA levels or the activities of 3-hydroxy-3-methylglutaryl coenzyme-A reductase and cholesterol ester hydrolase-rate-limiting enzymes for the de novo and deesterification pathways, respectively, for cholesterol formation in syncytiotrophoblasts in culture. Collectively, these results indicate that estrogen regulates the P450scc component of the progesterone biosynthetic pathway, which we suggest signals functional/biochemical differentiation of syncytiotrophoblasts during primate pregnancy. |
| Estrogen-mediated increases in LDL cholesterol and foam cell-containing lesions in human ApoB100xCETP transgenic mice Zuckerman, S. H., G. F. Evans, et al. (1999), Arterioscler Thromb Vasc Biol 19(6): 1476-83. Abstract: The murine double transgenic mouse expressing both human apoB100 and cholesteryl ester transfer protein (CETP), has been used as a model to understand the effects mediated by various therapeutic modalities on serum lipoproteins and on atherosclerotic lesion progression. In the present study the effects of estrogen therapy on serum lipoproteins were investigated after mice were placed on an atherosclerotic diet. The daily oral administration of 20 or 100 microg/kg of 17 alpha-ethinyl estradiol resulted in a significant, dose-dependent increase in LDL cholesterol over a 20-week regimen. These differences were apparent by 6 weeks and further increases were observed through the 20-week period. Although CETP did result in a reduction in total HDL, estrogen did not have any impact on the amount of CETP activity associated with the HDL particles. The significant increase in LDL cholesterol was associated with increases in the amount of apoB100 and B48 and apoE-containing particles. Hepatic apoB message levels, however, were not different between the experimental groups. Although the extent of atherosclerotic lesions was modest, <0.5% of the aortic surface area in the vehicle group, the high-dose estrogen group, showed an increase in lesion area consistent with the elevation in LDL cholesterol. These lesions, primarily restricted to the aortic root and aortic semilunar valves, were more intensely stained with Oil Red O in the high-dose estrogen group when compared with the vehicle controls. |
| Estrogen-mediated mitochondrial cholesterol transport and metabolism to pregnenolone in the rabbit luteinized ovary Cok, S. J., R. V. Hay, et al. (1997), Biol Reprod 57(2): 360-6. Abstract: We investigated the mechanisms of luteotropic actions of estradiol on steroidogenesis. To this end, we examined, in vitro, the metabolism of cholesterol from endogenous or exogenous sources for pregnenolone production in rabbit luteinized ovarian cell mitochondria isolated from pseudopregnant animals in various states of stimulation by estradiol. We found that estradiol-mediated regulation of mitochondrial cholesterol metabolism for pregnenolone production differs from the mechanisms of regulation reported for steroidogenic protein/polypeptide hormones in the following respects: 1) in the estradiol-sensitive, luteinized-ovary, rabbit model, temporary blockage of cytochrome P-450 cholesterol side-chain cleavage enzyme by aminoglutethimide treatment in vivo has no effect on mitochondrial pregnenolone production in vitro after the aminoglutethimide is removed, indicating no additional capacity for upstream cholesterol storage; 2) preincubating mitochondria at 37 degrees C fails to increase subsequent pregnenolone synthesis in response to the addition of isocitrate; and 3) exogenously added cholesterol does not readily enter the steroidogenic pool of cholesterol unless the endogenous cholesterol pool is first depleted. These new observations indicate that estradiol increases the usable steroidogenic cholesterol pool in rabbit ovarian mitochondria. Also, 1) they are consistent with a putative requirement for the participation of one or more estrogen-sensitive protein factors to enhance cholesterol trafficking to the inner mitochondrial membrane, and 2) they complement the observation of estrogen-dependent expression of steroidogenic acute regulatory protein in rabbit luteal tissue. |
| Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease Herrington, D. M., T. D. Howard, et al. (2002), N Engl J Med 346(13): 967-74. Abstract: BACKGROUND: Sequence variants in the gene encoding estrogen receptor alpha (ER-alpha) may modify the effects of hormone-replacement therapy on levels of high-density lipoprotein (HDL) cholesterol and other outcomes related to estrogen treatment in postmenopausal women. METHODS: We characterized 309 women with coronary artery disease who were enrolled in the Estrogen Replacement and Atherosclerosis trial with respect to eight previously described and two newly identified ER-alpha polymorphisms, and we examined the association between these polymorphisms and the response of HDL cholesterol and other lipids to treatment with estrogen alone or estrogen plus progestin. RESULTS: After adjustment for age, race, diabetes status, body-mass index, smoking status, alcohol intake, and frequency of exercise, the 18.9 percent of the women who had the IVS1-401 C/C genotype (i.e., with C on both chromosomes in intervening sequence 1 at position 401 before exon 2) had an increase in the HDL cholesterol level with hormone-replacement therapy that was more than twice the increase observed in the other women (13.1 mg per deciliter vs. 6.0 mg per deciliter, P for treatment-by-genotype interaction = 0.004); this effect was limited to changes in the HDL subfraction 3 (HDL3) (P for interaction=0.04). Similar patterns of response were observed for three other highly linked ER-alpha intron 1 polymorphisms close to the IVS1-401 site (range of P values for interaction = 0.07 to 0.005). The pattern of increased response of HDL cholesterol in women with the IVS1-401 C/C genotype was evident in both the women receiving estrogen and those receiving estrogen plus progestin, was preserved across racial and ethnic groups, and was significant among women who were compliant with the study medication (P<0.001). CONCLUSIONS: Postmenopausal women with coronary disease who have the ER-alpha IVS1-401 C/C genotype, or several other closely related genotypes, have an augmented response of HDL cholesterol to hormone-replacement therapy. |
| Ethanol enhances cholesterol synthesis and secretion in human hepatomal cells Visioli, F., S. Monti, et al. (1998), Alcohol 15(4): 299-303. Abstract: Excessive consumption of alcohol leads to severe alterations of lipid metabolism, including hyperlipemia and hypercholesterolemia. Following these epidemiological observations, we investigated the effects of ethanol at the cellular level by employing a human hepatomal cell line (HepG2) and by evaluating the biosyntheses of lipid classes from different labeled precursors. Incubation of cells with 2% ethanol resulted in a decreased labeling of phospholipids and in an increase in cholesterol synthesis and secretion. Triglyceride synthesis was increased by ethanol but their secretion in the medium was reduced, suggesting that these alterations may be related to their accumulation in the liver. The alcohol-induced alterations of lipid metabolism are not due to its metabolite acetaldehyde and data suggest that alcohol enhances cholesterol synthesis by affecting the initial steps without increasing HMGCoA expression. The observed modifications of lipid metabolism in HepG2 may partially explain the enhanced incidence of cardiovascular disorders that has been associated with alcoholism. |
| Ethanolamine plasmalogen and cholesterol reduce the total membrane oxidizability measured by the oxygen uptake method Maeba, R. and N. Ueta (2003), Biochem Biophys Res Commun 302(2): 265-70. Abstract: To investigate the effects of ethanolamine plasmalogen, phosphatidylethanolamine, cholesterol, and alpha-tocopherol on the oxidizability of membranes, various large unilamellar vesicles (LUVs) including these lipids and antioxidant were examined for their total membrane oxidizabilities, evaluated as R(p)/R(i)(1/2) value (where R(p) is rate of oxygen consumption and R(i)(1/2) is the square root of rate of chain initiation) by the oxygen uptake method with water-soluble radical initiator and inhibitor. Incorporation of bovine brain ethanolamine plasmalogen (BBEP) into vesicles as well as cholesterol led to lower the total membrane oxidizability dose-dependently. The effect of BBEP was more efficient in the presence of cholesterol in vesicles. On the other hand, diacyl counterpart, egg yolk phosphatidylethanolamine, and a typical radical scavenger, alpha-tocopherol, had no effect on the membrane oxidizability. Alpha-tocopherol only prolonged an induction period dose-dependently in the present oxidizing system, suggesting a novel antioxidant mechanism of ethanolamine plasmalogens besides the action of scavenging radicals. |
| Ethanolamine plasmalogens prevent the oxidation of cholesterol by reducing the oxidizability of cholesterol in phospholipid bilayers Maeba, R. and N. Ueta (2003), J Lipid Res 44(1): 164-71. Abstract: The aims of the present study are to establish an appropriate system for assessing the oxidizability of cholesterol (CH) in phospholipid (PL) bilayers, and to explore the effect of ethanolamine plasmalogens on the oxidizability of CH with the system, through comparing with those of choline plasmalogens, phosphatidylethanolamine, and antioxidant alpha-tocopherol (Toc). Investigation of the effects of oxidants, vesicle lamellar forms, saturation level, and constituent ratio of PLs in vesicles on CH oxidation revealed the suitability of a system comprising unilamellar vesicles and the water-soluble radical initiator 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH). As CH oxidation in the system was found to follow the rate law for autoxidation without significant interference from oxidizable PLs, the oxidizability of CH in PL bilayers could be experimentally determined from the equation: k (p)/(2k (t))(1/2)=R (p)/LHR(i)(1/2) by measuring the rate of CH oxidation. It was found with this system that bovine brain ethanolamine plasmalogen (BBEP), bovine heart choline plasmalogen, and egg yolk phosphatidylethanolamine lower the oxidizability of CH in bilayers. Comparison of the dose-dependent effects of each PL demonstrated the greatest ability of BBEP to reduce the oxidizability. A time course study of CH oxidation suggested a novel mechanism of BBEP for lowering the oxidizability of CH besides the action of scavenging radicals. |
| Ethanolamine plasmalogens protect cholesterol-rich liposomal membranes from oxidation caused by free radicals Maeba, R., Y. Sawada, et al. (2002), Chem Phys Lipids 120(1-2): 145-51. Abstract: The aim of the present study is to investigate the effect of ethanolamine plasmalogens on the oxidative stability of cholesterol-rich membranes by comparing it with that of diacyl glycerophosphoethanolamine, using bovine brain ethanolamine plasmalogen (BBEP) or egg yolk phosphatidylethanolamine (EYPE)-containing large unilamellar vesicles (LUVs) and the water-soluble radical initiator AAPH. Electron microscopic observation and particle size measurement visually demonstrated that ethanolamine plasmalogens protect cholesterol-rich phospholipid bilayers from oxidative collapse. Lipid analyses suggested that the effect of ethanolamine plasmalogens in stabilizing membranes against oxidation is partly due to the antioxidative action of plasmalogens involved in scavenging radicals at vinyl ether linkage. |
| Ethanol-extracted soy protein isolate does not modulate serum cholesterol in golden Syrian hamsters: a model of postmenopausal hypercholesterolemia Lucas, E. A., D. A. Khalil, et al. (2001), J Nutr 131(2): 211-4. Abstract: Soy protein consumption has been linked to reduction in hypercholesterolemia, a risk for coronary heart disease. However, to what extent soy protein itself or its non-nutritive components, e.g., isoflavones and saponins, exert this cholesterol-lowering effect requires further investigation. To evaluate the effect of the protein component alone on lipid variables, ethanol-extracted, isoflavone-depleted soy protein isolate (SPe) was studied in ovarian hormone-deficient hamsters. Forty-eight 6-month-old female Golden Syrian hamsters were either sham-operated or ovariectomized and fed casein-based or SPe-based diets for 70 d. Ovariectomy, but not protein source, significantly (P < 0.05) increased serum phospholipids and total, non-high density lipoprotein, free and esterified cholesterol concentrations. Serum HDL cholesterol concentrations were not altered with either treatment. No significant differences were observed in liver total lipids or liver total cholesterol among the groups. Soy protein isolate, however, lowered serum triglyceride concentrations in both sham-operated and ovariectomized hamsters. These findings confirm the ovariectomized hamster as a model of postmenopausal hypercholesterolemia. The results are consistent with earlier observations that isoflavones or other nonprotein components, perhaps in combination with soy protein, play an important role in exerting this hypocholesterolemic effect. Further studies are needed to investigate whether isolated nonprotein components of soy would be able to prevent the ovarian hormone deficiency-associated rise in serum cholesterol regardless of dietary protein source. |
| Ethanol-extracted soy protein isolate results in elevation of serum cholesterol in exogenously hypercholesterolemic rats Ni, W., S. Yoshida, et al. (1999), Lipids 34(7): 713-6. Abstract: Soy protein preparations were reported to have hypocholesterolemic actions in experimental animals and humans, while the active components and the mechanism by which this occurs are not clarified yet. The objective of this study is to address these issues by using exogenously hypercholesterolemic rats which are susceptible to dietary cholesterol. Two groups of five rats (male, 12-wk-old) were fed on AIN 93G-based diet with soy protein isolate (SPI) or ethanol-extracted SPI (EE-SPI) for 2 wk. EE-SPI was prepared by ethanol extraction to remove isoflavones and other components. Concentrations of serum and liver total cholesterol were lower in rats fed SPI than in those fed EE-SPI. The abundances of mRNA for 7alpha-hydroxylase and low density lipoprotein receptor in the liver were lower in EE-SPI group than those in SPI group. These results suggest that the ethanol extract from SPI has a factor(s) to alleviate hypercholesterolemia by increasing the removal of cholesterol from serum through the receptor pathway and then from liver through enhancement of bile acid synthesis. |
| Ethmoid cholesterol granuloma Armengot, M., R. Barona, et al. (1993), Otolaryngol Head Neck Surg 109(4): 762-5. |
| Ethnic differences in total and HDL cholesterol concentrations: Caucasians compared with predominantly Punjabi Sikh Indo-Asians Gama, R., A. B. Elfatih, et al. (2002), Ann Clin Biochem 39(Pt 6): 609-11. Abstract: BACKGROUND: In comparison with Caucasians, Indo-Asians resident in the UK have similar total cholesterol but lower HDL cholesterol (HDLC) concentrations. It is however possible that cardiovascular risk factors may vary between culturally different Indo-Asians. METHODS: We present data on 223 Indo-Asians (129 men, 94 women) and 787 Caucasians (421 men, 366 women) in whom a laboratory-based coronary heart disease (CHD) risk score calculation had been requested. RESULTS: Total cholesterol concentrations were similar in Indo-Asians and Caucasians. HDLC concentrations were higher (P < 0.001) in Caucasians 1.4 (1.3-1.4) mmol/L; median (95% confidence intervals) than in Indo-Asians 1.2 (1.2-1.3) mmol/L. Indo-Asian women 1.2 (1.2-1.3) mmol/L, Indo-Asian men 1.2 (1.2-1.3) mmol/L and Caucasian men 1.2 (1.2-1.3) mmol/L had similar HDLC concentrations but these were all lower (P < 0.001) than those in Caucasian women 1.4 (1.3-1.4) mmol/L. CONCLUSION: We confirm low HDLC concentrations in Indo-Asians, but propose that this is solely due to low HDLC concentrations in Indo-Asian women. Since Indo-Asians in Wolverhampton are predominantly Punjabi Sikhs, we suggest that the difference between this study and previous reports may be due to heterogeneity of CHD risk factors within culturally diverse Indo-Asians. |
| Etiologic significance of defects in cholesterol, phospholipid, and bile acid metabolism in the liver of patients with intrahepatic calculi Shoda, J., K. Oda, et al. (2001), Hepatology 33(5): 1194-205. Abstract: Intrahepatic calculi, highly prevalent in the Far East, including Japan, are characterized clinically by chronic proliferative cholangitis with frequent stone recurrences. Intrahepatic calculi consist of 2 groups, i.e., brown pigment stones, including a high cholesterol content, and cholesterol stones, with the former predominating. To gain insights into the pathogenesis of intrahepatic calculi, cholesterol and bile acid biosynthesis, as well as alterations in intracellular transport and/or canalicular secretion of phospholipid and bile acid were investigated in liver of patients with intrahepatic calculi. Enzyme activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were increased (12.8 +/- 1.9 pmol/min/mg protein, mean +/- SEM vs. 5.5 +/- 0.4 in controls; P <.01) and cholesterol 7 alpha-hydroxylase activities were decreased (1.3 +/- 0.4 vs. 4.9 +/- 0.6; P <.01) in liver specimens of patients with brown pigment stones. In addition, messenger RNA (mRNA) levels of multidrug resistance P-glycoprotein 3 (MDR3 Pgp) and phosphatidylcholine transfer protein (PCTP) were markedly low in the liver specimens compared with the levels in specimens of control subjects, gallbladder stone patients, and patients with obstructive cholestasis. The protein levels and the immunohistochemical staining were decreased for MDR3 Pgp and PCTP in the liver. Consistently, the concentrations of phospholipid were markedly reduced in the hepatic bile from both affected and unaffected hepatic segments. In patients with intrahepatic calculi, biliary cholesterol supersaturation and the formation of cholesterol-rich brown pigment as well as cholesterol stones may be attributed to decreased hepatic transport and biliary secretion of phospholipids, in the setting of increased cholesterogenesis and decreased bile acid synthesis. |
| Etiology and clinical presentation of cholesterol cholelithiasis Kajiyama, G. (2000), Nippon Naika Gakkai Zasshi 89(9): 1728-37. |
| Etiology and therapy of cholesterol cholelithiasis Tanaka, N. (1998), Nippon Naika Gakkai Zasshi 87(3): 475-9. |
| Etofibrate but not controlled-release niacin decreases LDL cholesterol and lipoprotein (a) in type IIb dyslipidemic subjects Sposito, A. C., A. P. Mansur, et al. (2001), Braz J Med Biol Res 34(2): 177-82. Abstract: Etofibrate is a hybrid drug which combines niacin with clofibrate. After contact with plasma hydrolases, both constituents are gradually released in a controlled-release manner. In this study, we compared the effects of etofibrate and controlled-release niacin on lipid profile and plasma lipoprotein (a) (Lp(a)) levels of patients with triglyceride levels of 200 to 400 mg/dl, total cholesterol above 240 mg/dl and Lp(a) above 40 mg/dl. These patients were randomly assigned to a double-blind 16-week treatment period with etofibrate (500 mg twice daily, N = 14) or niacin (500 mg twice daily, N = 11). In both treatment groups total cholesterol, VLDL cholesterol and triglycerides were equally reduced and high-density lipoprotein cholesterol was increased. Etofibrate, but not niacin, reduced Lp(a) by 26% and low-density lipoprotein (LDL) cholesterol by 23%. The hybrid compound etofibrate produced a more effective reduction in plasma LDL cholesterol and Lp(a) levels than controlled-release niacin in type IIb dyslipidemic subjects. |
| Etoposide treatment suppresses atherosclerotic plaque development in cholesterol-fed rabbits de la Llera-Moya, M., G. H. Rothblat, et al. (1992), Arterioscler Thromb 12(11): 1363-70. Abstract: To study the mechanisms by which monocytes/macrophages and smooth muscle cells contribute to atherosclerotic lesions, we studied atherosclerotic plaque formation in cholesterol-fed rabbits treated with etoposide, a drug that has been shown to have several effects that could interfere with the proposed interactions between these two cell types (M.W. Aarnoudes et al, Virchows Arch B 1984;47:211-216 and M. Rozencweig et al, Cancer 1977;40:334-342). Our results show that long-term etoposide treatment of New Zealand White rabbits maintained on a high-cholesterol diet decreases the extent of fatty streak formation in the aortic intima. Moreover, the plaques formed in the presence of etoposide are thinner and at least focally have less fibrous tissue and fewer smooth muscle cell-derived foam cells than do plaques in control rabbits. These effects are independent of the extent of the diet-induced hyperlipemia or an effect of etoposide on blood cell count and may be related to the inhibition of intimal cell proliferation by etoposide. |