| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Closing the gap: identification of human 3-ketosteroid reductase, the last unknown enzyme of mammalian cholesterol biosynthesis Marijanovic, Z., D. Laubner, et al. (2003), Mol Endocrinol 17(9): 1715-25. Abstract: The protein encoded by the HSD17B7 gene was originally described as a prolactin receptor-associated protein and as 17beta-hydroxysteroid dehydrogenase (HSD) type 7. Its ability to synthesize 17beta-estradiol in vitro has been reported previously. However, we demonstrate that HSD17B7 is the ortholog of the yeast 3-ketosteroid reductase Erg27p and converts zymosterone to zymosterol in vitro, using reduced nicotinamide adenine dinucleotide phosphate as cofactor. Expression of human and murine HSD17B7 in an Erg27p-deficient yeast strain complements the 3-ketosteroid reductase deficiency of the cells and restores growth on sterol-deficient medium. A fusion of HSD17B7 with green fluorescent protein is located in the endoplasmic reticulum, the site of postsqualene cholesterogenesis. Further critical evidence for a role of HSD17B7 in cholesterol metabolism is provided by the observation that its murine ortholog is a member of the same highly distinct embryonic synexpression group as hydroxymethyl-glutaryl-coenzyme A reductase, the rate-limiting enzyme of sterol biogenesis, and is specifically expressed in tissues that are involved in the pathogenesis of congenital cholesterol-deficiency disorders. We conclude that HSD17B7 participates in postsqualene cholesterol biosynthesis, thus completing the molecular cloning of all genes of this central metabolic pathway. In its function as the 3-ketosteroid reductase of cholesterol biosynthesis, HSD17B7 is a novel candidate for inborn errors of cholesterol metabolism. |
| Cluster significance analysis of the anticholesterolemic action of acyl-CoA cholesterol: acyltransferase inhibitors Ordorica Vargas, M. A., L. Velazquez Monroy Mde, et al. (2002), Proc West Pharmacol Soc 45: 79-81. |
| Clustering and six year cluster-tracking of serum total cholesterol, HDL-cholesterol and diastolic blood pressure in children and young adults. The Cardiovascular Risk in Young Finns Study Raitakari, O. T., K. V. Porkka, et al. (1994), J Clin Epidemiol 47(10): 1085-93. Abstract: Clustering and tracking of serum total cholesterol, high-density lipoprotein cholesterol (HDL-C) and diastolic blood pressure were studied in children and young adults. "High-risk" individuals were defined as those having these risk factors at the age and sex specific upper tertile (lowest tertile for HDL-C). Among older boys risk factors occurred at adverse levels more often than expected by chance. Cluster-tracking was assessed as the probability of remaining in the extreme tertiles during follow-up. Approximately 25% of subjects initially at "risk" remained there for 6 years. Subjects who became high-risk individuals during the follow-up expressed greater increase in obesity indices, started to consume more saturated fat and cholesterol and became physically active less often compared to those subjects who were initially at risk, but no longer at the follow-up. |
| Clustering of cholesterol in DMPC bilayers as indicated by membrane mechanical properties Hianik, T. and M. Haburcak (1993), Gen Physiol Biophys 12(3): 283-91. Abstract: Mechanical characteristics of bilayer lipid membranes (BLM) composed of dimyristoylphosphatidylcholine (DMPC) and cholesterol in the gel and liquid crystalline state were studied by measuring the modulus of elasticity in direction perpendicular to the BLM plane, E perpendicular. The value of E perpendicular varied nonmonotonically with the cholesterol concentration, with a maximum around c = 50 mol% cholesterol. E perpendicular of BLM in gel state was about 2 times higher than that measured for the liquid crystalline state but the shape of E perpendicular (c) curves was similar for both states of the membrane. This may be due to the formation of cholesterol clusters at c > 50 mol% in both phase states of BLM. |
| Clustering of high density lipoprotein cholesterol levels in premenopausal and postmenopausal female twins Harris, E. L., R. T. Falk, et al. (1993), Genet Epidemiol 10(6): 563-7. Abstract: Previous family and twin studies indicate that genetic variation makes an important contribution to individual variation in high density lipoprotein cholesterol (HDL) levels, even after adjustment for covariates (such as obesity and alcohol consumption) that also cluster in families. However, most studies assume that genetic mechanisms affecting variation in HDL level are the same in all subgroups of the population (e.g., men versus women, by age). Using data from the Kaiser-Permanente Women Twins Study, we found different patterns of clustering for monozygotic (MZ) and dizygotic (DZ) twins depending on menopausal status. Premenopausal MZ twins were more similar than postmenopausal MZ twins (r(i) = 0.79 and r(i) = 0.61, respectively, after adjustment for age, alcohol consumption, smoking status, degree of obesity, and leisure-time exercise); premenopausal and postmenopausal DZ twins were alike to the same extent (r(i) = 0.31 and r(i) = 0.32, respectively, adjusted as above). These data suggest that either postmenopausal MZ twins have a greater degree of shared environment than postmenopausal DZ twins (e.g., postmenopausal female hormone use) or that genetic mechanisms that affect individual variation in HDL level differ in pre- and postmenopausal women. Data were not available on postmenopausal female hormone use. If genetic mechanisms that influence variation in HDL levels differ between pre- and postmenopausal women, genetic epidemiologic methods that assume that genetic and environmental sources of variation are the same for all groups of individuals may lead to false conclusions. |
| CNS synaptogenesis promoted by glia-derived cholesterol Mauch, D. H., K. Nagler, et al. (2001), Science 294(5545): 1354-7. Abstract: The molecular mechanisms controlling synaptogenesis in the central nervous system (CNS) are poorly understood. Previous reports showed that a glia-derived factor strongly promotes synapse development in cultures of purified CNS neurons. Here, we identify this factor as cholesterol complexed to apolipoprotein E-containing lipoproteins. CNS neurons produce enough cholesterol to survive and grow, but the formation of numerous mature synapses demands additional amounts that must be provided by glia. Thus, the availability of cholesterol appears to limit synapse development. This may explain the delayed onset of CNS synaptogenesis after glia differentiation and neurobehavioral manifestations of defects in cholesterol or lipoprotein homeostasis. |
| Coaching patients with coronary heart disease to achieve the target cholesterol: a method to bridge the gap between evidence-based medicine and the "real world"--randomized controlled trial Vale, M. J., M. V. Jelinek, et al. (2002), J Clin Epidemiol 55(3): 245-52. Abstract: Community studies have demonstrated suboptimal achievement of lipid targets in the management of patients with coronary heart disease (CHD). An effective strategy is required for the application of evidence-based prevention therapy for CHD. The objective of this study was to test coaching as a technique to assist patients in achieving the target cholesterol level of <4.5 mmol/L. Patients with established CHD (n = 245) underwent a stratified randomization by cardiac procedure (coronary artery bypass graft surgery or percutaneous coronary intervention) to receive either the coaching intervention (n = 121) or usual medical care (n = 124). The primary outcome measure was fasting serum total cholesterol (TC), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and calculated low-density lipoprotein cholesterol (LDL-C) level, measured at 6 months post-randomization. At 6 months, the serum TC and LDL-C levels were significantly lower in the coaching intervention group (n = 107) than the usual care group (n = 112): mean TC (95%CI) 5.00 (4.82-5.17) mmol/L versus 5.54 (5.36-5.72) mmol/L (P <.0001); mean LDL-C (95%CI) 3.11 (2.94-3.29) mmol/L versus 3.57 (3.39-3.75) mmol/L (P <.0004), respectively. Coaching had no impact on TG or on HDL-C levels. Multivariate analysis showed that being coached (P <.001) had an effect of equal magnitude to being prescribed lipid-lowering drug therapy (P <.001). The effectiveness of the coaching intervention is best explained by both adherence to drug therapy and to dietary advice given. Coaching may be an appropriate method to reduce the treatment gap in applying evidence-based medicine to the "real world." |
| Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively Hunninghake, D., W. Insull, Jr., et al. (2001), Atherosclerosis 158(2): 407-16. Abstract: Colesevelam hydrochloride is a novel, potent, non-absorbed lipid-lowering agent previously shown to reduce low density lipoprotein (LDL) cholesterol. To examine the efficacy and safety of coadministration of colesevelam and atorvastatin, administration of these agents alone or in combination was examined in a double-blind study of 94 hypercholesterolemic men and women (baseline LDL cholesterol > or =160 mg/dl). After 4 weeks on the American Heart Association Step I diet, patients were randomized among five groups: placebo; colesevelam 3.8 g/day; atorvastatin 10 mg/day; coadminstered colesevelam 3.8 g/day plus atorvastatin 10 mg/day; or atorvastatin 80 mg/day. Fasting lipids were measured at screening, baseline and 2 and 4 weeks of treatment. LDL cholesterol decreased by 12-53% in all active treatment groups (P<0.01). LDL cholesterol reductions with combination therapy (48%) were statistically superior to colesevelam (12%) or low-dose atorvastatin (38%) alone (P<0.01), but similar to those achieved with atorvastatin 80 mg/day (53%). Total cholesterol decreased 6-39% in all active treatment groups (P<0.05). High density lipoprotein cholesterol increased significantly for all groups including placebo (P<0.05). Triglycerides decreased in patients taking atorvastatin alone (P<0.05), but were unaffected by colesevelam alone or in combination. The frequency of side effects did not differ among groups. At recommended starting doses of each agent, coadministration of colesevelam and atorvastatin was well tolerated, efficacious and produced additive LDL cholesterol reductions comparable to those observed with the maximum atorvastatin dose. |
| Coconut oil and sesame oil affect lymphatic absorption of cholesterol and fatty acids in rats Satchithanandam, S., M. Reicks, et al. (1993), J Nutr 123(11): 1852-8. Abstract: Five groups of male Wistar rats weighing approximately 200 g consumed 12 or 24% sesame oil or coconut oil diets or a control diet (14% corn oil) ad libitum for 4 wk. The thoracic ducts of these rats were cannulated, and a lipid emulsion containing 3Hcholesterol and 14Coleic acid was given through a duodenal catheter. Lymph was collected for 24 h and the isotopic tracers for cholesterol and fatty acid were measured. Rats fed the 24% sesame oil diet had significantly lower lymphatic cholesterol and fatty acid compared with the control group. Absorption of oleic acid in rats fed 24% coconut oil was significantly greater than in controls during 0-8 h but was not significantly different during 0-24 h. There were no differences among groups in the distribution of cholesterol and oleic acid either in the lymph lipoproteins or in the lipid classes. The significant reduction in lymph cholesterol and fatty acids due to sesame oil feeding may be an important factor in reducing hypercholesterolemia. |
| Co-cultivation of Niemann-Pick disease type C fibroblasts belonging to complementation groups alpha and beta stimulates LDL-derived cholesterol esterification Steinberg, S. J., D. Mondal, et al. (1996), J Inherit Metab Dis 19(6): 769-74. Abstract: Niemann-Pick disease type C (NPC) is a neurovisceral storage disorder with an unknown primary deficiency. Somatic cell hybridization experiments using human cultured fibroblasts have shown that two complementation groups (NPC-alpha and NPC-beta) are associated with the biochemical and clinical phenotypes comprising NPC. We identified the rarer complementation group NPC-beta originally using the technique of filipin staining as a marker for complementation. In this study we show that the esterification of cholesterol derived from the LDL pathway can be used as an isotopic assay. However, multinuclear hybrids exhibit a delayed induction in this pathway. Furthermore, we discovered that, in the presence of an LDL source, co-cultivation of fibroblasts belonging to NPC-alpha and NPC-beta stimulated cholesterol esterification. |
| Coenzyme Q10, alpha-tocopherol and free cholesterol in HDL and LDL fractions Johansen, K., H. Theorell, et al. (1991), Ann Med 23(6): 649-56. Abstract: Twenty-three randomly selected plasma samples from apparently healthy, middle aged men were analysed for coenzyme Q10 (CoQ10), alpha-tocopherol (AT) and free cholesterol (FC) in: 1) whole plasma, 2) the HDL lipoprotein fraction after LDL precipitation (VLDL + LDL). CoQ10, AT and FC in plasma averaged 0.69 +/-.11, 6.74 +/- 1.78 micrograms x ml-1 and 0.59 +/-.11 mg x ml-1 and in HDL 0.17, 3.24 micrograms x ml-1 and 0.17 mg x ml-1 or 29, 48 and 29% of plasma values. Amounts of CoQ10 and AT were correlated to that of FC in all pools. The amount of HDL-CoQ10 but not of HDL-AT fell, with the HDL-FC expressed as the fraction of plasma FC. In all pools, N-AT versus AT initially increased and then levelled off, indicating saturation like conditions in contrast to CoQ10. Thus, CoQ10 and AT are differently allocated in HDL and LDL. This might have a bearing both on the suggested lipoprotein protection against peroxidation by these two antioxidants, but also on the distribution and allocation in different organs of CoQ10 and AT by HDL and LDL transportation. |
| Coexistence of cholesterol tophi and calcium pyrophosphate deposit disease Modol, J. M., S. Holgado, et al. (1996), Med Clin (Barc) 106(17): 678-9. |
| Coexistence of increased levels of adiposity, insulin, and blood pressure in a young adult cohort with elevated very-low-density lipoprotein cholesterol: the Bogalusa Heart Study Srinivasan, S. R., W. Bao, et al. (1993), Metabolism 42(2): 170-6. Abstract: Clustering and interrelationships of elevated levels (> 75th percentile) of adiposity, insulin, blood pressure, and very-low-density lipoprotein cholesterol (VLDL-C) were examined in a selected subset (n = 89) of a young adult cohort aged 18 to 26 years, whose childhood (ages 10 to 18 years) VLDL-C and/or low-density lipoprotein cholesterol (LDL-C) levels were in the upper or lower percentiles of the distribution. Among the young adults with elevated VLDL-C and LDL-C levels, 23% had increased adiposity and systolic blood pressure, 17% had increased insulin levels and systolic blood pressure, 17% had increased insulin levels and adiposity, and 13% had increased insulin levels, adiposity, and systolic blood pressure; corresponding values among those with elevated VLDL-C and normal (< 75th percentile) LDL-C levels were 29%, 18%, 24%, and 18%. As adults, the group with elevated VLDL-C and LDL-C levels had increased adiposity (P =.02) and systolic blood pressure (P =.002) in comparison to those with normal VLDL-C and LDL-C levels, whereas the group with elevated VLDL-C and normal LDL-C levels had increased fasting plasma insulin levels (P =.05) and systolic blood pressure (P =.007). These 89 individuals had undergone a glucose tolerance test during childhood.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Coexisting endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary alveolar proteinosis in a pediatric population: a clinical, radiographic, and pathologic correlation Fisher, M., V. Roggli, et al. (1992), Pediatr Pathol 12(3): 365-83. Abstract: Benign pulmonary diseases that have been associated with the accumulation of endogenous lipids within the alveoli, bronchioles, and interstitial tissues include endogenous lipoid pneumonia (ELP), pulmonary alveolar proteinosis (PAP), pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG), various xanthomatous lesions, and malakoplakia. In ELP, fat-filled finely vacuolated macrophages fill the alveoli. In PAP, the aveoli become filled with cholesterol and periodic acid-Schiff (PAS)-positive acellular debris. In PICG, cholesterol esters are released from degenerating macrophages and, as organization occurs, the cholesterol is deposited in the form of acicular clefts within the interstitium. These morphologically distinct presentations of endogenous lipid deposition within the lung have long been thought to represent unique disease processes but several authors now postulate a possible relationship between these entities. We report here on the clinical, radiographic, and morphologic findings in eight pediatric patients with diverse primary disease processes who were subsequently found to have varying and often coexisting degrees of ELP, PAP, and PICG. |
| Coexpression of cholesterol sulfate and cytokeratin as tumor markers in well-differentiated squamous cell carcinoma of the human uterine cervix Kiguchi, K., M. Iwamori, et al. (1998), Clin Cancer Res 4(12): 2985-90. Abstract: The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker. |
| Co-expression of cholesteryl ester transfer protein and defective apolipoprotein E in transgenic mice alters plasma cholesterol distribution. Implications for the pathogenesis of type III hyperlipoproteinemia Fazio, S., K. R. Marotti, et al. (1994), J Biol Chem 269(51): 32368-72. Abstract: Despite the definite etiologic link between apolipoprotein (apo) E mutations and type III hyperlipoproteinemia (HLP), it is not clear what additional factors are involved in the development of florid hyperlipidemia and how to explain the wide variability in the expression of the hyperlipidemic phenotype in carriers of receptor binding-defective apoE variants. The present study was designed to determine whether the overexpression of cholesteryl ester transfer protein (CETP), a plasma protein that transfers cholesteryl esters from the high density lipoproteins (HDL) to the very low density lipoproteins (VLDL) and whose activity is increased in hyperlipidemic states, plays a role in the development of hyperlipidemia and beta-VLDL accumulation in type III HLP. We produced double-transgenic mice that co-expressed high levels of simian CETP and either high or low levels of a human receptor binding-defective apoE variant, apoE(Cys-142). We previously reported that apoE(Cys-142) high-expresser mice showed spontaneous hyperlipidemia and accumulation of beta-VLDL, whereas the low-expresser mice showed only a modest increase in VLDL cholesterol. Co-expression of CETP induced a massive transfer of cholesteryl esters from the HDL to the VLDL in both lines of double-transgenic mice. As a result, HDL cholesterol and apoA-I levels were reduced to about 50% of normal, VLDL cholesterol increased 2.5-fold, and the cholesteryl ester content of VLDL reached values similar to those observed in human beta-VLDL. The ratio of defective to normal apoE in VLDL was unaffected by CETP co-expression and was higher in animals expressing high apoE levels. Finally, in spite of an increased accumulation of beta-VLDL in the high-expresser mice, the VLDL of the low-expresser mice maintained pre-beta mobility upon co-expression of CETP. The results of this study demonstrate that the ratio of defective to normal apoE on the VLDL, rather than the cholesteryl ester content of VLDL, is the major factor determining the development of severe hyperlipidemia and the formation and accumulation of beta-VLDL in type III HLP. |
| Coffee and cholesterol Simo Minana, J. and M. Gaztambide Ganuza (1996), Med Clin (Barc) 107(12): 478. |
| Coffee and cholesterol, an Italian study Salvaggio, A., M. Periti, et al. (1991), Am J Epidemiol 134(2): 149-56. Abstract: In the present study, conducted in northern Italy between 1986 and 1989, the authors investigated the possible association between coffee consumption and serum cholesterol levels in 8,983 subjects, 7,432 men and 1,551 women, managers and employees aged 18-65 years, who were examined during a program of preventive medicine upon an agreement between various companies and the Centro Diagnostico Italiano. Analysis of covariance was used to compare the serum cholesterol levels of the subjects subdivided according to coffee consumption, along with age, body mass index, alcohol consumption, cigarette smoking, and physical activity. An important relation was demonstrated between coffee intake and cholesterol, particularly in the men, the differences in serum cholesterol in the coffee users compared with the nonusers being 6.1 +/- 1.4 (standard error) mg/dl for consumers of 1-3 cups/day (3.4 +/- 1.4 mg/dl after adjustment for age, body mass index, alcohol and cigarette consumption, and physical activity), 9.9 +/- 1.6 mg/dl for those drinking 4-5 cups/day (5.8 +/- 1.6 mg/dl after adjustment), and 14.8 +/- 2.0 mg/dl for those drinking over 5 cups/day (9.6 +/- 2.0 mg/dl after adjustment). This relation remained substantially unvaried when nonsmokers and smokers were analyzed separately. It has been suggested that it is coffee prepared by boiling rather than other methods that has a hypercholesterolemic effect. Our observations demonstrate an interesting relation between coffee and cholesterol, even though the coffee drunk in Italy is mainly filtered and nonboiled. However, our finding is not necessarily in disagreement with the above hypothesis since, when coffee is prepared in the Italian way (with the mocha method), ground coffee is preheated by steam and more importantly, the water passes through the ground coffee at a higher temperature than with the other brewing methods. |
| Coffee and cholesterol: what is brewing? Thelle, D. S. (1991), J Intern Med 230(4): 289-91. |
| Coffee and lipoprotein cholesterol Grossman, E. M. (1992), Am J Clin Nutr 56(3): 605-6. |