| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Redistribution of rabbit blood serum lipoproteins, caused by a one-time administration of cholesterol Bozhko, G. and V. M. Kulabukhov (1993), Biokhimiia 58(10): 1594-603. Abstract: The redistribution of rabbit blood serum lipoproteins following 24-hr incubation of the sera at 37 degrees C and after a single injection of cholesterol (0.2 g/kg) was studied. In both cases there was an increase in the intermediate density (IDL) and low density lipoproteins (LDL) and a sharp decrease in very low density lipoproteins (VLDL). The proportion of the total fraction of high density lipoproteins (HDL) decreased also. The redistribution of the HDL subpopulations against the background of the HDL decline after a single cholesterol dose seems to be due to a relative increase in HDL3 and a decrease in HDL2. The HDL transformation during heat incubation of control sera was accompanied by HDL3 conversion into HDL2. These data suggest that a single cholesterol dose and heat incubation of blood sera stimulate the direct and reverse cholesterol transport. In isolated sera these processes subside gradually. The inhibition mechanism entails the depletion of the lipoprotein system for chylomicrons and VLDL and exhaustion of HDL2. The restoration of the functional potential of the blood lipid-transporting system needs the exchange between lipoproteins and tissues. |
| Reduced activity of lecithin:cholesterol acyltransferase in the serum of cows with ketosis and left displacement of the abomasum Nakagawa, H. and N. Katoh (1998), Vet Res Commun 22(8): 517-24. Abstract: Lecithin:cholesterol acyltransferase (LCAT) activity was evaluated in sera from cows with ketosis and in some with left displacement of the abomasum (LDA) that occurred during early lactation. The enzyme activities of 652 +/- 214 U (mean +/- SD) in cows with ketosis (n = 6) and 683 +/- 110 U in those with LDA (n = 5) were significantly (p < 0.01) decreased compared to those in healthy normal cows (994 +/- 65 U, n = 8). Serum concentrations of free cholesterol, cholesteryl esters (CE) and phospholipids were similarly decreased in the two diseases. Cows whose LCAT activity and CE concentration were lower than the normal values were detected while in the non-lactating stage, and some of these cows had ketosis after parturition. It is suggested that evaluation of the LCAT activity and of the CE concentration during the non-lactating stage would be useful in detecting cows that are susceptible to postparturient disorders such as ketosis. |
| Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: clues to the biology of premature atherosclerosis in Hutchinson-Gilford Progeria Syndrome Gordon, L. B., I. A. Harten, et al. (2005), J Pediatr 146(3): 336-41. Abstract: OBJECTIVES: Children with Hutchinson-Gilford Progeria Syndrome (HGPS) die of severe premature atherosclerosis at an average age of 13 years. Although the LMNA gene defect responsible for this "premature aging syndrome" has been identified, biological mechanisms underlying the accelerated atherosclerosis are unknown. We determined whether children with HGPS demonstrate abnormalities in known biomarkers for cardiovascular disease (CVD) risk. STUDY DESIGN: We quantified serum lipids, lipoproteins, C-reactive protein (CRP), and adiponectin in children with HGPS and age-matched control children. RESULTS: HDL cholesterol (P <.0001) and adiponectin (P <.001) concentrations decreased significantly with increasing age in HGPS but not in control children. There was a positive correlation between these variables in HGPS (P <.0001) but not control children. Mean total cholesterol, LDL and HDL cholesterol, triglyceride, and median CRP levels were similar between HGPS and control children (all P >.05). CONCLUSIONS: Declining HDL cholesterol and adiponectin with advancing age may contribute to accelerated atherosclerotic plaque formation in HGPS. Several factors frequently associated with CVD risk in normal aging (elevated CRP, total and LDL cholesterol) showed no difference and are unlikely to influence CVD risk in HGPS. HDL and adiponectin may represent significant mediators and potential therapeutic targets for atherosclerosis in HGPS. |
| Reduced and high molecular weight barley beta-glucans decrease plasma total and non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters Wilson, T. A., R. J. Nicolosi, et al. (2004), J Nutr 134(10): 2617-22. Abstract: Consumption of concentrated barley beta-glucan lowers plasma cholesterol because of its soluble dietary fiber nature. The role of molecular weight (MW) in lowering serum cholesterol is not well established. Prior studies showed that enzymatic degradation of beta-glucan eliminates the cholesterol-lowering activity; however, these studies did not evaluate the MW of the beta-glucan. The current study was conducted to evaluate whether barley beta-glucan concentrates, partially hydrolyzed to reduce MW, possess cholesterol-lowering and antiatherogenic activities. The reduced MW fraction was compared with a high MW beta-glucan concentrate from the same barley flour. Concentrated beta-glucan preparations were evaluated in Syrian Golden F(1)B hamsters fed a hypercholesterolemic diet (HCD) with cholesterol, hydrogenated coconut oil, and cellulose. After 2 wk, hamsters were fed HCD or diets that contained high or reduced MW beta-glucan at a concentration of 8 g/100 g at the expense of cellulose. Decreases in plasma total cholesterol (TC) and non-HDL-cholesterol (non-HDL-C) concentrations occurred in the hamsters fed reduced MW and high MW beta-glucan diets. Plasma HDL-C concentrations did not differ. HCD-fed hamsters had higher plasma triglyceride concentrations. Liver TC, free cholesterol, and cholesterol ester concentrations did not differ. Aortic cholesterol ester concentrations were lower in the reduced MW beta-glucan-fed hamsters. Consumption of either high or reduced MW beta-glucan increased concentrations of fecal total neutral sterols and coprostanol, a cholesterol derivative. Fecal excretion of cholesterol was greater than in HCD-fed hamsters only in those fed the reduced MW beta-glucan. Study results demonstrate that the cholesterol-lowering activity of barley beta-glucan may occur at both lower and higher MW. |
| Reduced atherosclerosis in hormone-sensitive lipase transgenic mice overexpressing cholesterol acceptors Choy, H. A., X. P. Wang, et al. (2003), Biochim Biophys Acta 1634(3): 76-85. Abstract: Macrophage-specific overexpression of cholesteryl ester hydrolysis in hormone-sensitive lipase transgenic (HSL Tg) female mice paradoxically increases cholesterol esterification and cholesteryl ester accumulation in macrophages, and thus susceptibility to diet-induced atherosclerosis compared to nontransgenic C57BL/6 mice. The current studies suggest that whereas increased cholesterol uptake could contribute to transgenic foam cell formation, there are no differences in cholesterol synthesis and the expression of cholesterol efflux mediators (ABCA1, ABCG1, apoE, PPARgamma, and LXRalpha) compared to wild-type macrophages. HSL Tg macrophages exhibit twofold greater efflux of cholesterol to apoA-I in vitro, suggesting the potential rate-limiting role of cholesteryl ester hydrolysis in efflux. However, macrophage cholesteryl ester levels appear to depend on the relative efficacy of alternate pathways for free cholesterol in either efflux or re-esterification. Thus, increased atherosclerosis in HSL Tg mice appears to be due to the coupling of the efficient re-esterification of excess free cholesterol to its limited removal mediated by the cholesterol acceptors in these mice. The overexpression of cholesterol acceptors in HSL-apoA-IV double-transgenic mice increases plasma HDL levels and decreases diet-induced atherosclerosis compared to HSL Tg mice, with aortic lesions reduced to sizes in nontransgenic littermates. The results in vivo are consistent with the effective efflux from HSL Tg macrophages supplemented with HDL and apoA-I in vitro, and highlight the importance of cholesterol acceptors in inhibiting atherosclerosis caused by imbalances in the cholesteryl ester cycle. |
| Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways Bjorkbacka, H., V. V. Kunjathoor, et al. (2004), Nat Med 10(4): 416-21. Abstract: Atherosclerosis, the leading cause of death in developed countries, has been linked to hypercholesterolemia for decades. More recently, atherosclerotic lesion progression has been shown to depend on persistent, chronic inflammation in the artery wall. Although several studies have implicated infectious agents in this process, the role of infection in atherosclerosis remains controversial. Because the involvement of monocytes and macrophages in the pathogenesis of atherosclerosis is well established, we investigated the possibility that macrophage innate immunity signaling pathways normally activated by pathogens might also be activated in response to hyperlipidemia. We examined atherosclerotic lesion development in uninfected, hyperlipidemic mice lacking expression of either lipopolysaccharide (LPS) receptor CD14 or myeloid differentiation protein-88 (MyD88), which transduces cell signaling events downstream of the Toll-like receptors (TLRs), as well as receptors for interleukin-1 (IL-1) and IL-18. Whereas the MyD88-deficient mice evinced a marked reduction in early atherosclerosis, mice deficient in CD14 had no decrease in early lesion development. Inactivation of the MyD88 pathway led to a reduction in atherosclerosis through a decrease in macrophage recruitment to the artery wall that was associated with reduced chemokine levels. These findings link elevated serum lipid levels to a proinflammatory signaling cascade that is also engaged by microbial pathogens. |
| Reduced cellular cholesterol content in peroxisome-deficient fibroblasts is associated with impaired uptake of the patient's low density lipoprotein and with reduced cholesterol synthesis Mandel, H., M. Getsis, et al. (1995), J Lipid Res 36(6): 1385-91. Abstract: Mammalian cells acquire cellular cholesterol by de novo synthesis as well as by uptake of low density lipoprotein (LDL). Peroxisomes contain enzymes involved in the synthesis of cholesterol, and peroxisome-deficient (PD) patients have been shown to have hypocholesterolemia and abnormal LDL. We therefore decided to study whether cholesterol synthesis and cellular uptake of LDL are impaired in cultured PD fibroblasts. The present study demonstrates a significantly lower cellular cholesterol mass in fibroblasts from three PD patients, as compared to control cells (41-59% of controls). The rate of cholesterol synthesis was also reduced in all three PD cell lines, being 16-20% of the control values. LDL binding and degradation by fibroblasts were 3- to 5-fold higher in the PD cells as compared to control cells. Similarly, enrichment of normal fibroblasts with tetracosanoic acid (C-24:0), a situation that could mimic the in vivo accumulation of very long chain fatty acid (VLCFA) in PD cells, caused LDL binding and degradation to be 4-fold higher than in non-treated cells. On the other hand, the uptake of LDL derived from PD patients by normal fibroblasts was markedly reduced (by up to 67%) in comparison to the cellular uptake of normal LDL. Similar results were obtained in PD cells. This study demonstrates a lower cellular cholesterol content and reduced cholesterol synthesis rate in PD cell lines. In addition, we demonstrate that regulation of the uptake of normal LDL by cellular LDL receptors is operative in PD cells, whereas LDL derived from PD patients is not recognized normally by the LDL receptor.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Reduced cholesterol absorption in hamsters by crilvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor Hajri, T., F. Chanussot, et al. (1997), Eur J Pharmacol 320(1): 65-71. Abstract: Crilvastatin, a new drug from the pyrrolidone family, has been previously shown to inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in vitro and in vivo, to reduce the absorption of dietary cholesterol and to stimulate the activity of cholesterol 7 alpha-hydroxylase in the rat. The aim of this study was to evaluate the effects of crilvastatin on cholesterol and bile acid metabolism in the hamster. In hamsters fed on a lithogenic diet for 8 weeks, crilvastatin treatment (200 mg/day per kg body weight) did not change plasma lipid levels, failed to improve bile parameters and did not prevent gallstone formation. In hamsters fed on a basal cholesterol-rich (0.2%) diet for 8 weeks, crilvastatin at the same dose reduced the cholesterol level in the plasma by 20%, with a decrease of both low-density and high-density lipoprotein cholesterol. The drug did not significantly stimulate the biliary secretion of bile acids but significantly decreased the activity of acyl coenzyme A:cholesterol acyltransferase in the small intestine by 64%. This effect was enhanced when cholestyramine, a bile acid-sequestering resin, was given in combination with crilvastatin. Crilvastatin alone did not change the activity of cholesterol 7 alpha-hydroxylase in the liver, despite the marked reduction in both hepatic cholesterogenesis and intestinal absorption of dietary cholesterol (the absorption coefficient was 44 +/- 2% in treated hamsters vs. 61 +/- 7% in controls). |
| Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1 van der Veen, J. N., J. K. Kruit, et al. (2005), J Lipid Res 46(3): 526-34. Abstract: Peroxisome proliferator-activated receptors (PPARs) control the transcription of genes involved in lipid metabolism. Activation of PPARdelta may have antiatherogenic effects through the increase of plasma HDL, theoretically promoting reverse cholesterol transport from peripheral tissues toward the liver for removal via bile and feces. Effects of PPARdelta activation by GW610742 were evaluated in wild-type and Abca1-deficient (Abca1(-/-)) mice that lack HDL. Treatment with GW610742 resulted in an approximately 50% increase of plasma HDL-cholesterol in wild-type mice, whereas plasma cholesterol levels remained extremely low in Abca1(-/-) mice. Yet, biliary cholesterol secretion rates were similar in untreated wild-type and Abca1(-/-) mice and unaltered upon treatment. Unexpectedly, PPARdelta activation led to enhanced fecal neutral sterol loss in both groups without any changes in intestinal Abca1, Abcg5, Abcg8, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase expression. Moreover, GW610742 treatment resulted in a 43% reduction of fractional cholesterol absorption in wild-type mice, coinciding with a significantly reduced expression of the cholesterol absorption protein Niemann-Pick C1-like 1 (Npc1l1) in the intestine. PPARdelta activation is associated with increased plasma HDL and reduced intestinal cholesterol absorption efficiency that may be related to decreased intestinal Npc1l1 expression. Thus, PPARdelta is a promising target for drugs aimed to treat or prevent atherosclerosis. |
| Reduced cholesterol accumulation and improved deficient peroxisomal functions in a murine model of Niemann-Pick type C disease upon treatment with peroxisomal proliferators Schedin, S., P. Pentchev, et al. (1998), Biochem Pharmacol 56(9): 1195-9. Abstract: Niemann-Pick type C disease is an inherited disorder characterized by lysosomal accumulation of cholesterol and the mutant gene has recently been identified. The predicted gene product is a transmembrane protein showing homology to proteins involved in the regulation of cholesterol homeostasis, such as 3-hydroxy-3-methylglutaryl-coenzyme A and the sterol regulatory element binding protein cleavage-activating protein. Recent investigations have established a peroxisomal deficiency, which raised the question of whether peroxisomal proliferation could affect this cholesterol-processing error. Mutant mice with Niemann-Pick type C disease were treated with the peroxisomal inducer perfluorooctanoic acid, which increased peroxisomal beta-oxidation and catalase activity to the same level as in control mice. Not only the peroxisomal, but also the lysosomal malfunctions were corrected and the cholesterol content was decreased. Clofibrate, another peroxisomal inducer, restored both peroxisomal enzyme activities and ubiquinone content. It appears that in Niemann-Pick type C disease treatment with appropriate peroxisomal inducers restores basic cellular functions, indicating a relationship between peroxisomes and cholesterol homeostasis, and thereby may effectively interfere with the development of the disease. |
| Reduced cholesterol efflux to mildly oxidized high density lipoprotein Morel, D. W. (1994), Biochem Biophys Res Commun 200(1): 408-16. Abstract: Mild oxidation (< 6h) of human high density lipoprotein (HDL) induced by incubation with copper ions increased its thiobarbituric acid reactivity, decreased its phospholipid content, increased its free cholesterol to phospholipid ratio and reduced its ability to mediate cholesterol efflux from cells. While protein modification did occur with further oxidation (> 12h), diminished efflux of cell cholesterol was apparent for HDL samples without increased electrophoretic mobility or altered apolipoproteins. Thus, reduced cholesterol efflux to mildly oxidized HDL may reflect changes in its lipids rather than its apoproteins. By limiting cholesterol removal from cells, any mild oxidation of HDL which might occur in vivo could contribute to cellular cholesterol accumulation. |
| Reduced cholesterol esterification in CaCo-2 cells by indirect action of pravastatin Reimann, F. M., F. Winkelmann, et al. (1996), Atherosclerosis 125(1): 63-70. Abstract: In microsomal preparations of CaCo-2 cells pravastatin decreased cholesterol esterifying activity at 25 micrograms/ml to 82.5% and at 800 micrograms/ml to 56.2% of controls. Pravastatin reduced cholesteryl ester formation dose-dependently also in viable CaCo-2 cells. However, the maximal inhibition was by 90.4% at pravastatin concentration of 25 micrograms/ml, half maximal inhibition occurred between concentrations of 5 and 10 micrograms/ml. Addition of mevalonolactone, which serves as endogenous source of cholesterol, antagonized this effect. At 10 mM mevalonolactone (MVL) even doses up to 200 micrograms/ml of pravastatin were ineffective. On the other hand, pravastatin suppressed cholesteryl ester formation when acyl-CoA cholesterol acyltransferase (ACAT) (E.C. 2.3.1.26) activity was stimulated by addition of exogenous liposomal or Low Density Lipoprotein (LDL)-derived cholesterol. This inhibition was refractory to increasing amounts of exogenous cholesterol up to 400 micrograms/ml. Therefore we conclude that only excessive doses of pravastatin suppress ACAT activity directly. In viable cells the observed inhibition of cholesteryl ester formation is due to the block in de novo synthesis of cholesterol, causing a lack of substrate for ACAT and of non-sterol products of mevalonic acid. Furthermore pravastatin interferes with the esterification and/or intracellular transport only of exogenous cholesterol, confirming former results of a compartmentalized cholesterol metabolism in the enterocyte. |
| Reduced cholesterol in women. Wrong therapy after drug information Larsson, A., L. Werko, et al. (1994), Lakartidningen 91(46): 4280-1. |
| Reduced cholesterol is associated with recent minor illness: the CARDIA Study. Coronary Artery Risk Development in Young Adults Jacobs, D. R., Jr., B. Hebert, et al. (1997), Am J Epidemiol 146(7): 558-64. Abstract: Lower levels of plasma total cholesterol have been observed during severe infection, but it is not known whether the minor illnesses encountered in the general population are also associated with reduced cholesterol. This paper examines the relation between minor illness and plasma lipids, using 7- and 10-year follow-up data from more than 3,000 generally healthy participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. At both 7 and 10 years, approximately 8.5% of participants stated they had been "ill with cold, flu, fever, or vomiting in the past 24 hours." In both cross-sectional and longitudinal analyses, the plasma total cholesterol was about 5 mg/dl lower (p < 0.006) and high density lipoprotein cholesterol about 1.2 mg/dl lower (p < 0.12) in those who reported minor illness than in those who did not. Plasma triglycerides did not vary with minor illness. The authors conclude that reductions in plasma total, low density, and high density lipoprotein cholesterol mark an acute phase response even during minor illness. These reductions may bias surveys over a limited geographic area during a short period because the proportion with minor illness may vary locally. Because this effect should be stronger with more precise illness diagnosis, clinicians should avoid making measurements for cholesterol management when illness may alter plasma lipid levels and the resulting decisions. |
| Reduced cholesterol levels in African-American adults with sickle cell disease Shores, J., J. Peterson, et al. (2003), J Natl Med Assoc 95(9): 813-7. Abstract: In a recent study of boys and girls with sickle cell disease (SCD) in Nigeria, a common finding with this genetic hematologic disorder was a marked reduction in total cholesterol. Epidemiologic studies have identified a relation between low serum levels of total cholesterol (< 130 mg/dL) and increased mortality from all causes. We were interested in knowing if hypocholesterolemia was present in African-American adults with SCD. We therefore compared the plasma lipid profiles of the 16 men and 20 women with SCD who received care at the University of Texas Medical Branch at Galveston between 1996 and 2001 with those of 2,415 gender-matched African Americans who were seen at the same hospital but who did not have SCD. The age-adjusted mean total cholesterol concentrations of the SCD males and females were 147 +/- 42 mg/dL and 179 +/- 36 mg/dL, compared to male and female control values of 200 +/- 75 mg/dL and 216 +/- 61 mg/dL, respectively. These differences between SCD subjects and controls were statistically significant (p < 0.001). The LDL-cholesterol levels of the men and women with SCD (68 +/- 28 mg/dl and 95 +/- 33 mg/dl, respectively) were also significantly reduced relative to the controls (121 +/- 58 mg/dl and 128 +/- 54 mg/dl, respectively, p = 0.001). The triglyceride levels of the men with SCD were much reduced relative to the male controls (102 +/- 34 mg/dL versus 194 +/- 215 mg/dL, p = 0.02), but were not different between the SCD females and their control group. The HDL-cholesterol levels of the SCD subjects and the controls were not different. These results indicate that total cholesterol and LDL-cholesterol concentrations are significantly reduced in adult men and women with SCD in the United States, and should heighten interest in the implication that low levels of cholesterol might exacerbate the medical problems inherent in this genetic disease. |
| Reduced cholesterol metastability of hepatic bile and its further decline in gall bladder bile in patients with cholesterol gall stones Nakano, K. and K. Chijiiwa (1993), Gut 34(5): 702-7. Abstract: The reduced metastability of biliary cholesterol in the gall bladder bile of patients with cholesterol gall stones has been well shown. The purpose of this study was to examine the hypothesis that such a difference in metastability already exists in hepatic bile. Paired hepatic and gall bladder bile samples were collected from 10 patients with cholesterol gall stones and six patients without gall stones. Cholesterol nucleation time, biliary lipid concentration, vesicular cholesterol distribution, and biliary protein concentration were measured and compared. The nucleation time in the hepatic bile of patients with cholesterol gall stones was significantly shorter than the gall stone free patients (8.2 (7.2) v 15.7 (5.8) days, p < 0.05), and was associated with a greater concentration of biliary lipid despite the lack of a difference in the cholesterol saturation index (CSI) and total protein concentration. During the storage of bile in the gall bladder, the nucleation time became quicker in the patients with cholesterol gall stone (2.9 (1.7) days) while it was similar in the gall stone free patients (17.3 (5.7) days) compared with that of the corresponding hepatic bile. These differences were associated with a higher CSI (1.44 (0.33) v 1.13 (0.14), p < 0.05) and a greater vesicular cholesterol distribution (19.7 (11.9) v 4.4 (1.4)%, p < 0.01) in the patients with cholesterol gall stones than the gall stone free patients. The concentrations of total lipid and protein in gall bladder bile were not significantly different between the two groups. In conclusion, patients with cholesterol gall stones produce less metastable hepatic bile by the evidence of shorter nucleation time. During the storage of the bile in the gall bladder, the metastability is reduced further only in the cholesterol gall stone patients but not in the gall stone free patients. |
| Reduced digestibility of beef tallow and cocoa butter affects bile acid excretion and reduces hepatic esterified cholesterol in rats Monsma, C. C., D. D. Gallaher, et al. (1996), J Nutr 126(8): 2028-35. Abstract: We investigated stearic acid (18:0) digestibility and how it affects bile acid excretion in male Sprague-Dawley rats fed diets containing (g 18:0/ 100 g fatty acids): pork lard (13); beef tallow (19); cocoa butter (35); corn oil (2) or corn oil plus cholestyramine for 25 d. Apparent lipid digestibility was reduced with increased dietary intake of 18:0 as follows: lard (90%), beef tallow (82%), cocoa butter (78%), cholestyramine (87%), and corn oil (94%); P < 0.001, pooled SD = 2. Hepatic concentrations of total and esterified cholesterol were significantly less in cocoa butter-, beef tallow- and cholestyramine-fed groups compared with lard- and corn oil-fed groups. Fecal bile acid excretion was significantly greater in rats fed cocoa butter or cholestyramine compared with those fed corn oil. The half-life of intraperitoneally administered 14C-cholic acid was significantly longer in rats fed cocoa butter (1.36 +/- 0.02 d) compared with cholestyramine (0.98 +/- 0.03 d) and intermediate in those fed corn oil, lard or beef tallow (1.11-1.21 +/- 0.05 d). Fecal excretion of muricholic acids (bile acids) correlated strongly with dietary intake of 18:0 (r2 = 0.98, P < 0.01), whereas excretion of bile acids derived from cholic and chenodeoxycholic acids was similar among groups. In summary, the lower digestibility of cocoa butter is associated with increased fecal bile acid excretion, reduced hepatic concentration of esterified cholesterol, decreased fractional turnover of 14C-cholic acid and increased excretion of muricholic acids in rats. The mechanism by which stearate-rich dietary fats alter bile acid and cholesterol metabolism is, however, uncertain. |
| Reduced frequency of high cholesterol levels among patients with intracerebral haemorrhage Thrift, A., J. McNeil, et al. (2002), J Clin Neurosci 9(4): 376-80. Abstract: To determine whether a relationship exists between high cholesterol levels and intracerebral haemorrhage (ICH) a case-control study was undertaken on 331 consecutive cases of first-episode primary ICH, verified by computed tomography, and 331 age- and sex-matched community controls. Using conditional logistic regression the adjusted odds ratio (OR) of ICH among individuals reporting a high cholesterol level was 0.45 95% confidence interval (CI), 0.28-0.73. A similar finding was observed when the analysis was limited to those using cholesterol-lowering drugs (OR 0.25; 95% CI, 0.08-0.80). These data provide support for an inverse relationship between high cholesterol levels and ICH. When considered together with previous findings, in which low cholesterol levels have been associated with an increased risk of haemorrhagic stroke, these data provide evidence that this inverse relationship may extend into a higher range of cholesterol values. |
| Reduced HDL2 cholesterol subspecies and elevated postheparin hepatic lipase activity in older men with abdominal obesity and asymptomatic myocardial ischemia Katzel, L. I., P. J. Coon, et al. (1992), Arterioscler Thromb 12(7): 814-23. Abstract: Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60 +/- 7 years, mean +/- SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio WHR), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162 +/- 71 versus 102 +/- 39 mg/dl, p less than 0.001) and lower HDL-C (33 +/- 6 versus 37 +/- 7 mg/dl, p less than 0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p less than 0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34 +/- 8 versus 27 +/- 10 mumol/ml.hr-1, p less than 0.03) and was correlated with log insulin area (r = 0.36, p less than 0.05) and WHR (r = 0.32, p less than 0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r = -0.46, p less than 0.01, n = 41) as well as WHR (r = -0.49, p less than 0.001, n = 47) and log insulin area (r = -0.37, p less than 0.05, n = 47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL2 subspecies levels may predispose these older men to atherosclerosis. |
| Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice Agellon, L. B., A. Walsh, et al. (1991), J Biol Chem 266(17): 10796-801. Abstract: The human cholesteryl ester transfer protein (CETP) facilitates the exchange of neutral lipids among lipoproteins. In order to evaluate the effects of increased plasma CETP on lipoprotein levels, a human CETP minigene was placed under the control of the mouse metallothionein-I promoter and used to develop transgenic mice. Integration of the human CETP transgene into the mouse genome resulted in the production of active plasma CETP. Zinc induction of CETP transgene expression caused depression of serum cholesterol due to a significant reduction of high density lipoprotein cholesterol. There was no change in total cholesterol content in very low and low density lipoproteins. However, there was a decrease in the free cholesterol/cholesteryl ester ratio in plasma and in all lipoprotein fractions of transgenic mouse plasma, suggesting stimulation of plasma cholesterol esterification. The results suggest that high levels of plasma CETP activity may be a cause of reduced high density lipoproteins in humans. |