| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Conformation of apolipoprotein AI in reconstituted lipoprotein particles and particle-membrane interaction: effect of cholesterol Tricerri, A., B. Corsico, et al. (1998), Biochim Biophys Acta 1391(1): 67-78. Abstract: Discoidal recombinant high density lipoproteins (rHDL) of apolipoprotein AI (apoAI) and palmitoyloleoylphosphatidylcholine (POPC), with or without cholesterol, were prepared by cholate dialysis. By gel filtration, rHDL containing 2-4 (Lp2, Lp3 and Lp4) apoAI molecules/particle were obtained. The ApoAI conformation in these rHDL was investigated by tryptophan fluorescence, denaturation with guanidine HCl, and immunoreactivity with two monoclonal antibodies recognizing epitopes in the N-terminal and central domains. Data show that apoAI conformation is highly dependent on particle size as well as on cholesterol. The ability of rHDL to interact with lipid bilayer was studied by measuring leakage induction on POPC and POPC/cholesterol vesicles loaded with terbium/dipicolinic acid. Among the cholesterol-free rHDL, the most efficient ones were the smallest Lp2. Leakage induction on POPC vesicles is dramatically decreased by the presence of cholesterol in Lp2 and Lp3. All the rHDL, but specially those containing cholesterol, induced more leakage on the POPC/cholesterol than on the POPC vesicles. These results suggest that in small cholesterol-poor particles, apoAI could have a conformation determining a high affinity for membranes, which could facilitate cholesterol efflux. After cholesterol enrichment, a conformational change in apoAI could decrease the affinity for membranes allowing the lipoprotein release. |
| Conformation of phosphatidylcholine in neat and cholesterol-containing liquid-crystalline bilayers. Application of a novel method Eklund, K. K., J. A. Virtanen, et al. (1992), Biochemistry 31(36): 8560-5. Abstract: The conformation of phosphatidylcholine in liquid-crystalline bilayers was studied with a novel, high-resolution method employing phosphatidylcholine species containing pyrenyl moieties in both acyl chains of variable length. Analysis of the intramolecular pyrene-pyrene collision data obtained for 30 such species in terms of a simple geometrical model showed that the sn-1 acyl chain penetrates, on the average, 0.84 +/- 0.11 methylene units (0.8 A) deeper into the bilayer than the sn-2 chain at 22 degrees C. A similar value was obtained at 37 degrees C. Since the penetration difference of the sn-1 and sn-2 acyl chains is inherently coupled to the conformation of the glycerol moiety, these data mean that the glycerol moiety of phosphatidylcholine is, on the average, only moderately tilted with respect to the bilayer plane in the liquid-crystalline state. This contrasts the perpendicular orientation observed previously for phosphatidylcholine crystals Pearson, R. H., & Pascher, I. (1979) Nature 281, 499-501. Importantly, addition of 50 mol % cholesterol, which is known to reduce dramatically the interactions between phosphatidylcholine molecules in bilayers, had only a small effect on the penetration difference of the acyl chains, strongly suggesting that the conformation of phosphatidylcholine in the liquid-crystalline state is determined largely by intramolecular, rather than intermolecular, interactions. |
| Conformational analysis of amphotericin B--cholesterol channel complex Silberstein, A. (1998), J Membr Biol 162(2): 117-26. Abstract: A molecular model of ionic channel formed by flexible molecules of amphotericin B and cholesterol is proposed. Complexes with axial symmetry from 5 to 11 were simulated. In contrast to the model of the channel formed from rigid molecules, flexible molecules form a tightly packed structure consolidated by both dispersive forces and intermolecular hydrogen bonds. Contributions of a lactone ring, polar heads, cholesterol and lipid environments to the global energy of the complex formation are discussed. Among the complexes capable of ionic transport, that of axial symmetry eight is preferable. Two types of complexes, differing by the number of intramolecular hydrogen bonds, are shown to be possible. |
| Conformational changes of the alpha 1-proteinase inhibitor affecting its cholesterol binding ability Janciauskiene, S. and S. Eriksson (1993), FEBS Lett 323(3): 236-8. Abstract: The effect of conformational changes of the alpha 1-proteinase inhibitor (alpha 1PI) on alpha 1PI-cholesterol complex (1:2 mol/mol) formation in vitro was studied with electrophoretic and gel chromatographic methods. Native alpha 1PI was modified by adding free thiol agents such as glutathione, cysteine HCl, or DL-homocysteine, by heating, or by cleavage with pancreatic elastase or trypsin. Conformational changes of the alpha 1PI molecule induced by these procedures were all accompanied by a loss of its ability to bind cholesterol in vitro under standard experimental conditions. The data suggest alpha 1PI-cholesterol binding to be affected by both direct and indirect modifications of the alpha 1PI-reactive center, that is situated on a mobile peptide loop. |
| Congenic BB.SHR rat provides evidence for effects of a chromosome 4 segment (D4Mit6-Npy approximately 1 cm) on total serum and lipoprotein lipid concentration and composition after feeding a high-fat, high-cholesterol diet Kovacs, P., J. van den Brandt, et al. (2001), Metabolism 50(4): 458-62. Abstract: Congenic BB.SHR (previously referred to as BB.LL) rats were generated by transferring the segment of chromosome 4 flanked by the D4Mit6 and Spr loci from the spontaneously hypertensive rat (SHR/Mol) onto the genetic background of the diabetes-prone BB/OK rat. In this study, the influence of the above-mentioned region of chromosome 4 on triglyceride, cholesterol, and phospholipid phenotypes after a high-fat, high-cholesterol diet was examined by comparison of BB.SHR congenic rats with BB/OK rats. BB/OK and BB.SHR had comparable concentrations of basal and postdietary serum insulin, as well as of basal total serum triglycerides and had an identical body weight and food intake at the beginning of the test period. However, after 4 weeks on the test diet, BB.SHR rats were significantly heavier than BB/OK rats and had significantly higher food intake and lower total serum triglyceride concentrations. The basal serum leptin level was significantly lower, but postdietary serum leptin concentration did not show a significant difference between the 2 strains. Furthermore, significantly higher basal total serum cholesterol and phospholipid levels were observed in BB.SHR rats, but this difference disappeared after feeding the high-fat, high-cholesterol diet. Postdietary high-density lipoprotein (HDL)(2) cholesterol and phospholipid levels were significantly elevated in BB.SHR rats when compared with BB/OK rats. The 2 strains also differed slightly, but significantly, with respect to the other HDL phospholipid concentrations. In addition to previously described differences between BB/OK and BB.SHR rats, the results of this study clearly show the impact of genes, lying within the transferred segment, on serum lipid phenotypes after high-fat, high-cholesterol diet. |
| Congenital brain anomalies in distal cholesterol biosynthesis defects Hennekam, R. C. (2005), J Inherit Metab Dis 28(3): 385-92. Abstract: Cholesterol is known to be a significant constituent of the central nervous system. It also plays an important role in developmental pathways to form the human brain, such as the Sonic Hedgehog pathway. Disturbances in the formation of cholesterol may therefore be expected to cause brain malformations and brain dysfunctions. Here a short review of the consequences of defects of the distal cholesterol pathways to brain formation and functioning is provided. |
| Congenital cholesteatoma and cholesterol granuloma of the temporal bone: role of magnetic resonance imaging Pisaneschi, M. J. and B. Langer (2000), Top Magn Reson Imaging 11(2): 87-97. Abstract: Magnetic resonance imaging (MRI) can be of significant benefit in characterizing expansile lesions of the petrous apex. MRI can be of particular help in distinguishing congenital cholesteatoma from cholesterol granuloma. Furthermore, with the advent of faster high-resolution scanning techniques, MRI can define precise spatial relationships of these masses with the middle and inner ear structures, internal carotid artery, jugular vein, and other structures of the skull base. MRI scanning is sensitive in detecting intracranial extension of these masses. MR angiography can provide additional information regarding the relationship of these masses with adjacent vascular structures and confirm patency of the adjacent vessels. In the postoperative period, MR scanning can help evaluate for complete removal, complication, recurrence, or formation of complicating granulation tissue. |
| Conicity index and waist-hip ratio and their relationship with total cholesterol and blood pressure in middle-aged European and migrant Pakistani men Bose, K. and C. G. Mascie-Taylor (1998), Ann Hum Biol 25(1): 11-6. Abstract: A comparative study of abdominal adiposity, total cholesterol (TC), systolic (SBP) and diastolic blood pressure (DBP) in middle-aged European (n = 262) and mainly migrant Pakistani (n = 100) men of Mirpuri (Kashmiri) origin found no significant ethnic difference in mean body mass index (BMI), waist-hip ratio (WHR) and conicity index (CI). However, Pakistanis had significantly lower mean TC (p < 0.0001) and SBP (p < 0.005) but significantly higher mean (p < 0.05) DBP. Correlations of WHR and CI with age, BMI, TC, SBP and DBP were not significantly different within and between the two ethnic groups. However, multiple regression analysis revealed that Pakistanis had significantly lower cholesterol and systolic blood pressure for any given CI or WHR but no ethnic difference was observed for diastolic blood pressure. There is no evidence from this study that CI shows any advantage over WHR, as a surrogate for abdominal adiposity, in cross-sectional epidemiological investigation of risk factors for coronary heart disease (CHD) in ethnic groups like South Asians. |
| Conjoint high triglycerides and low HDL cholesterol across generations. Analysis of proband hypertriglyceridemia and lipid/lipoprotein disorders in first-degree family members Sprecher, D. L., M. J. Hein, et al. (1994), Circulation 90(3): 1177-84. Abstract: BACKGROUND: To discern whether hypertriglyceridemia (hyper-TG, TG > 95th percentile) and hypoalphalipoporteinemia (hypoalpha, high-density lipoprotein HDL-C < or = 10th percentile) are jointly transmitted in families, we studied 385 probands with marked elevations in TG or cholesterol levels (TG or cholesterol > 99th percentile in a previous visit) and their 2072-first-degree relatives in the Lipid Research Clinics' Family Study. Repeat TG measurement, with exclusion criterion of TG < or = 95th percentile, resulted in 162 probands with hyper-TG. METHODS AND RESULTS: When the proband demonstrated the conjoint trait (CT; ie, TG > 95th percentile, HDL-C < or = 10th percentile, n = 82), an average of 10.6% of first-degree relatives conjointly expressed hyper-TG and hypoalpha in contrast to only 4.1% of first-degree relatives of a proband who expressed high TG levels with normal HDL-C levels (TG > 95th percentile, HDL-C > 10th percentile, n = 80). Hyper-TG was expressed in 24.2% of first-degree relatives of probands with CT. However, hyper-TG was expressed in only 14.4% of first-degree degree relatives of probands with hyper-TG alone. CT probands and their family members tended to have more reported cardiac events and symptoms (P =.02 and.09, respectively) than those subjects associated with hyper-TG alone. CONCLUSIONS: The differences in HDL-C-TG abnormalities between families related to hyper-TG probands with or without hypoalpha indicate that bottom decile HDL-C is not simply secondary to hyper-TG. A familial interaction is suggested between HDL-C and TG levels consistent with the transmission of hyper-TG and hypoalpha among first-degree relatives. Among subjects and their families with hyper-TG, those who in addition have low HDL-C demonstrate a tendency for more coronary artery disease than do those with normal HDL-C levels. |
| Conjugated linoleic acid and atherosclerosis: no effect on molecular markers of cholesterol homeostasis in THP-1 macrophages Weldon, S., S. Mitchell, et al. (2004), Atherosclerosis 174(2): 261-73. Abstract: Macrophage cholesterol homeostasis is a key process involved in the initiation and progression of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) regulate the transcription of the genes involved in cholesterol homeostasis and thus represent an important therapeutic target in terms of reducing atherosclerosis. Conjugated linoleic acid (CLA) is a potent anti-atherogenic dietary fatty acid in animal models of atherosclerosis and is capable of activating PPARs in vitro and in vivo. Therefore, this study examined whether the anti-atherogenic effects of CLA in vivo could be ascribed to altered cholesterol homeostasis in macrophages and macrophage derived foam cells. Of several genes that regulate cholesterol homeostasis investigated, CLA had most effect on the class B scavenger receptor CD36. The cis-9,trans-11 CLA (c9,t11-CLA) and trans-10,cis-12 CLA (t10,c12-CLA) isomers augmented CD36 mRNA expression (P<0.001). Confocal laser microscopy characterised the three-dimensional expression patterns of CD36 in THP-1 macrophages. Linoleic acid, CLA and the PPARgamma ligand rosiglitazone increased discrete cell surface CD36 localisation, with a heterogeneous punctate pattern of expression. In agreement with the observed increases in CD36 mRNA and cell surface expression, intracellular cholesterol concentrations were greater in macrophages exposed to linoleic acid and CLA. Further analysis of cholesterol metabolism showed that CLA had no effect on THP-1 derived foam cell cholesterol efflux to apo AI. Thus, altered cholesterol homeostasis in the macrophage may not explain the anti-atherogenic effects of CLA observed in vivo. |
| Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury Adachi, J., K. Ishii, et al. (2003), Arch Toxicol 77(6): 353-7. Abstract: It is our hypothesis that as a consequence of increased oxidative stress, rats develop lung injury with increased cholesterol-derived hydroperoxides and oxysterols in lung after consecutive exposure of the rats to paraquat. To test this we administered 10 mg/kg of paraquat i.p. once or seven times (once a day) to Wistar rats. Rats were killed, and lung tissue was collected 24 h after the last paraquat injection. We found that in response to consecutive paraquat doses, there were significant increases in 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH; P=0.01) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH; P=0.01), and 7-ketocholesterol (7-keto; P=0.03). In addition, pulmonary hemorrhage, thickening of alveolar septum, and inflammatory cell infiltration of macrophages were observed. This is the first report showing enhanced cholesterol peroxidation and lung injury of rats due to consecutive doses of paraquat. |
| Consensus concerning triglycerides and high-density lipoprotein-cholesterol in the United States Gevers Leuven, J. A. (1992), Ned Tijdschr Geneeskd 136(39): 1891-3. |
| Consensus on cholesterol Hammond, J. and R. J. Rona (1991), Bmj 302(6786): 1209. |
| Consensus statement of King's Fund Forum: blood cholesterol measurement in the prevention of coronary heart disease Smith, J. P. (1990), J Adv Nurs 15(1): 1-2. |
| Consequences of cellular cholesterol accumulation: basic concepts and physiological implications Tabas, I. (2002), J Clin Invest 110(7): 905-11. |
| Consequences of the National Cholesterol Education Program Froom, J. and P. Froom (1990), J Fam Pract 30(5): 533-6. |
| Consideration of serum cholesterol in risk factor profiling for all young individuals Berenson, G. S. and S. R. Srinivasan (2001), Nutr Metab Cardiovasc Dis 11 Suppl 5: 1-9. Abstract: AIM: To alter the adverse natural course of coronary artery disease and its risk factors, primary prevention should begin in childhood. DATA SYNTHESIS: High serum cholesterol, LDL cholesterol (LDL-C) in particular, remains the major determinant of atherosclerotic process beginning in childhood. Selective cholesterol screening of children based on family history is inadequate. Tracking of childhood elevated cholesterol in conjunction with other risk factors into adulthood argues in favor of universal screening in the young. Further, individual adverse levels of LDL-C not only increase the incidence of adulthood dyslipidemia, but also markedly enhances the prevalence of obesity and hypertension seen in the adult population. CONCLUSIONS: Screening of all young individuals for serum cholesterol along with a cardiovascular risk factor profile is recommended. Cardiovascular disease remains a public health issue and identifying young individuals at risk is basic to prevention. |
| Consistency between US dietary fat intake and serum total cholesterol concentrations: the National Health and Nutrition Examination Surveys Ernst, N. D., C. T. Sempos, et al. (1997), Am J Clin Nutr 66(4 Suppl): 965S-972S. Abstract: The National Health and Nutrition Examination Surveys (NHANESs) are conducted periodically to assess the health and nutritional status of the US population by means of standardized interviews and physical examinations. Since the early 1970s there have been three national cross-sectional surveys: NHANES I, 1971-1974; NHANES II, 1976-1980; and NHANES III, phase 1, 1988-1991. During the 18 y between the midpoint of NHANES I (1972) and the midpoint of phase 1 of NHANES III (1990), the age-adjusted mean percentage of energy from fat declined from 36.4% to 34.1% for adults aged 20-74 y. Trend data are shown for dietary fat and cholesterol as well as for serum cholesterol from NHANES I (1971-1975) to NHANES III (1988-1991) by age, sex, and race-ethnicity. The results document a decline in dietary fat, saturated fat, dietary cholesterol, and serum cholesterol. The observed changes reflect those that are predicted by the classic Keys and Hegsted formulas. Changes in reported intake are matched by similar shifts in the food supply for sources of these nutrients. These changes suggest that the Healthy People 2000 goal of reducing the mean serum cholesterol concentration of US adults to < or = 200 mg/dL (5.17 mmol/L) is attainable. The changes in diet are promising, yet we are challenged to achieve greater reductions in the intake of total fat and saturated fatty acids. |
| Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples Chien, K. L., H. C. Hsu, et al. (2003), BMC Genet 4(1): 7. Abstract: BACKGROUND: Triglyceride/HDL cholesterol ratio (TG/HDL-C) is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C. RESULTS: Two populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs) and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs) were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0). Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 +/- 0.114, p = 0.002), but the common shared environmental factor was higher in hospital-based families (0.203 +/- 0.042, p < 0.001). Commingling analyses showed that more than one-component distribution models were the best-fit models to explain the variance in both populations. Complex segregation analysis by regressive models revealed that in both samples the best-fit model of TG/HDL-C was the model of environmental effects plus familial correlation, in which significant parent-offspring and sibling correlations were demonstrated. Models of major gene effects were rejected in both samples. CONCLUSION: Variations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families. |
| Consistently high plasma high-density lipoprotein-cholesterol levels in children in Spain, a country with low cardiovascular mortality Garces, C., A. Gil, et al. (2004), Metabolism 53(8): 1045-7. Abstract: Coronary heart disease (CHD) mortality is relatively low in Spain compared with other developed countries and has remained low despite an apparent increase in mean plasma cholesterol concentration in adults over the last several years. It is accepted that pathologic processes related to arteriosclerosis development begin in childhood and seem to be related to the presence of cardiovascular risk factors at this age. High-density lipoprotein-cholesterol (HDL-C) levels in children have been inversely correlated with the incidence of coronary heart disease in the different countries studied. Childhood plasma lipoprotein profile might contribute to the low coronary heart disease mortality in Spain. Thus, we analyzed data on lipid levels over time in schoolchildren in Spain in the last decade. Plasma lipid levels were analyzed in prepuberal children (6 to 8 years) in 3 school-based surveys performed by our group in Madrid in 1987, 1993, and 1999. A significant increase in plasma total cholesterol (P <.05) and low-density lipoprotein-cholesterol (LDL-C) (P <.01) levels in prepuberal children was observed over the last decade. However, the mean concentration of plasma HDL-C remained stable and very high. These high levels of plasma HDL-C in Spanish school children may help to explain why the coronary heart disease mortality rate in Spain is low compared with that in other developed countries. |