| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Does serum cholesterol contribute to vertebral bone loss in postmenopausal women? Tanko, L. B., Y. Z. Bagger, et al. (2003), Bone 32(1): 8-14. Abstract: Recent in vitro and animal studies suggest that cholesterol and its metabolites inhibit the functional activity of osteoblasts and thereby induce reduced bone mineralization. However, scant information is available on the clinical implication of these findings with special regard to postmenopausal bone loss. Therefore, the aim of the present study was to investigate cross-sectional and longitudinal associations between serum cholesterol, bone mineral density (BMD), and bone turnover in 340 postmenopausal women aged 50-75 years (mean 59 years), who were followed for 8.3 +/- 1.1 years. BMD in the lumbar spine, distal forearm, and total hip was measured by dual energy X-ray absorptiometry. Other study variables were physical measures, serum cholesterol, serum markers of bone turnover, and self-reported information on various risk factors for osteoporosis. At baseline, serum cholesterol showed significant negative correlation with BMD at the lumbar spine (r = -0.21, P < 0.0001) and distal forearm (r = -0.14, P = 0.013), but not at the hip. No associations of serum cholesterol with serum osteocalcin (r = 0.054, P = 0.317) and CTX (r = -0.027, P = 0.623) were, however, noted. After adjustment for age and BMI, the negative correlation remained significant at the lumbar spine (r = -0.16, P = 0.004), but not at the distal forearm (r = -0.018, P = 0.738). At the end of the 8-year follow-up, the correlation between serum cholesterol and spine BMD was not observed. Those with the largest increases in serum cholesterol, however, showed the greatest decreases in spine BMD independently of the changes in BMI (r = -0.16, P = 0.004). The correlation between the changes in serum cholesterol and the simultaneous changes in osteocalcin (r = 0.081, P = 0.140) and CTX (r = 0.042, P = 0.441) were statistically insignificant. Thus, our results suggest that the weak associations between spine BMD and serum cholesterol can be explained by the fact that both variables are simultaneously affected by estrogen deficiency rather than by a direct influence of serum cholesterol on osteoblast function. |
| Does skin cholesterol testing provide benefit? Ho, C. (2002), Issues Emerg Health Technol(34): 1-4. Abstract: Cholesterol 1,2,3 9 (TM) is being promoted as a non-invasive way to measure cholesterol that has accumulated in a person's skin. The test received a medical device licence from Health Canada in January 2001. It was approved by the U.S. Food and Drug Administration (FDA) in June 2002. This test is not intended to be used as a screening tool for coronary artery disease in the general population. Evidence from non-randomized, non-blinded clinical trials suggests a correlation between higher skin cholesterol levels and the presence of severe coronary arterial lesions. At this point, technical improvements and more robust evidence are required to determine the significance of this technology in clinical practice. |
| Does the cholesterol content in blood cells depend on its level in plasma? Klimov, A. N., L. E. Vasil'eva, et al. (1994), Biokhimiia 59(1): 69-77. Abstract: The cholesterol content in human erythrocytes, granulocytes and the total leucocyte fraction with varying levels of plasma cholesterol has been studied. There was no correlation between the cell cholesterol content and the levels of total, LDL and HDL cholesterol in the plasma. The mean cholesterol content in one cell has been found to be equal to 1.26 x 10(-13) g in the erythrocytes, 2.08 x 10(-12) g in the granulocytes and 3.35 x 10(-12) g in the total leucocyte fraction. |
| Does the HMG-CoA reductase inhibitor pravastatin influence nucleation of cholesterol crystals in supersaturated model bile? Smit, J. W., K. J. Van Erpecum, et al. (1996), Eur J Gastroenterol Hepatol 8(3): 197-200. Abstract: OBJECTIVE: To assess whether the presence in bile of HMG-CoA reductase inhibitors, which are secreted predominantly into the bile, influences biliary lithogenicity. DESIGN: Physiologic biliary concentrations of the hydrophilic HMG-CoA reductase inhibitor pravastatin were added to supersaturated model bile (cholesterol saturation index 1.4) and vesicles, the latter with and without the concomitant addition of the nucleation-promoting bile salt taurodeoxycholate. OUTCOME MEASURES: Nucleation time, defined as the number of days after which cholesterol monohydrate crystals are visible by phase contrast microscopy in filtered samples of model bile and vesicles, was assessed. RESULTS: The addition of pravastatin 0.01-1 mg/ml did not influence the nucleation time of supersaturated model bile (mean nucleation time without pravastatin: 8.3 +/- 2.2 days (SD), with pravastatin 1 mg/ml 9.3 +/- 0.4 days and pravastatin 0.01 mg/ml 7.6 +/- 2.3 days). The addition of similar concentrations of pravastatin to vesicle fractions alone did not influence nucleation time (> 20 days), nor could it prevent the nucleation-promoting effect of taurodeoxycholate (nucleation time with or without pravastatin 1 day). CONCLUSION: The results from this in-vitro study indicate that the presence of pravastatin in bile may not influence gallbladder bile lithogenicity. It can be hypothesized that this also applies to other HMG-CoA reductase inhibitors. |
| Does the level of LDL cholesterol moderate a relationship between DRD4 and novelty seeking? Elovainio, M., M. Kivimaki, et al. (2005), Biol Psychol 68(1): 79-86. Abstract: This study examined the role of low density lipoprotein (LDL) cholesterol level in the association between Dopamine D4 receptor (DRD4) polymorphism and temperament dimension novelty seeking. From the on-going population based study of "Cardiovascular Risk in Young Finns", 78 men and women responded to the novelty seeking scale of the temperament and character inventory Archives of General Psychiatry 44 (1987) 573 and were apolipoprotein E (apoE) and DRD4 genotyped. DRD4 polymorphism was related to disorderliness, a component of novelty seeking, in subjects with high LDL cholesterol level but not in subjects with low LDL cholesterol level. This finding did not change after adjustment for apoE polymorphism. Our findings suggest that the genetic determination of temperament may be dependent on biological factors, such as LDL cholesterol. |
| Does thrombolysis produce cholesterol embolisation? Mendia, R., G. D'Aloya, et al. (1992), Lancet 339(8792): 562. |
| Does vibration cause poststenotic dilatation in vivo and influence atherogenesis in cholesterol-fed rabbits? Gow, B. S., M. J. Legg, et al. (1992), J Biomech Eng 114(1): 20-5. Abstract: Arterial post-stenotic dilatation (PSD) is a fusiform swelling immediately down-stream to a stenosis. It is characterized by the presence of turbulent blood flow and wall vibration which has been claimed by others to be causal by producing structural weakening. We tested the hypothesis that vibration causes PSD in vivo by attaching electromagnetic and pneumatic vibrators to the aortic wall in chronic rabbits. We also observed whether mechanical vibration of the aorta in vivo influenced the distribution of oil-red-O lesions during one percent dietary cholesterol feeding. Low mass vibration gauges were developed to measure the vibration. Electromechanical vibrators having a ceramic magnet slug within a coil supplied with 50 Hz were glued to the aorta of chronic rabbits and the vibration maintained for an average of 8 weeks. Despite greater amounts of energy imparted to the wall there was no dilatation or difference in oil-red-O staining from the controls. Five weeks vibration at 100 Hz and an amplitude equal to the normal diameter pulse also produced no dilatation. We conclude that vibration does not cause PSD in vivo and suggest that its cause is likely to involve the vascular muscle stimulated by the effect of turbulent flow on the endothelium. |
| Does VLDL-LDL-cholesterol in cord serum predict future level of lipoproteins? Fonnebo, V., L. B. Dahl, et al. (1991), Acta Paediatr Scand 80(8-9): 780-5. Abstract: Lipoproteins were measured in 618 healthy, full-term newborns. Seventy-four with a VLDL-LDL-cholesterol above 1.3 mmol/l (50 mg/dl) at birth and 25 randomly chosen controls with VLDL-LDL-cholesterol 1.3 mmol/l or below at birth were followed up at age 2. Seventy-two (52 in the high VLDL-LDL-cholesterol group and 20 in the low VLDL-LDL-cholesterol group) were followed up at age 13. At age 2 mean total cholesterol was 5.48 mmol/l (SEM 0.10) in the children with a high VLDL-LDL-cholesterol at birth, compared to 4.69 mmol/l (SEM 0.17) in the children with a low VLDL-LDL-cholesterol at birth (p less than 0.001). A difference was still present at age 13 (4.74 mmol/l; SEM 0.11 versus 4.20 mmol/l; SEM 0.14; p less than 0.01). At age 13 apolipoprotein B was 0.74 g/l (SEM 0.02) in the children with a high VLDL-LDL-cholesterol at birth, compared to 0.65 g/l (SEM 0.02) in the children with a low VLDL-LDL-cholesterol at birth (p less than 0.01). Children with high VLDL-LDL-cholesterol at birth might be more liable to high lipoprotein serum levels later in life. |
| Doing the right thing: stop worrying about cholesterol Kessler, G. (1994), Circulation 90(5): 2573. |
| Doing the right thing: stop worrying about cholesterol Ravnskov, U. (1994), Circulation 90(5): 2572-3; author reply 2573-7. |
| Domain formation in sphingomyelin/cholesterol mixed membranes studied by spin-label electron spin resonance spectroscopy Collado, M. I., F. M. Goni, et al. (2005), Biochemistry 44(12): 4911-8. Abstract: Interactions of palmitoylsphingomyelin with cholesterol in multilamellar vesicles have been studied over a wide range of compositions and temperatures in excess water by using electron spin resonance (ESR) spectroscopy. Spin labels bearing the nitroxide free radical group on the 5 or 14 C-atom in either the sn-2 stearoyl chain of phosphatidylcholine (predominantly 1-palmitoyl) or the N-stearoyl chain of sphingomyelin were used to determine the mobility and ordering of the lipids in the different phases. Two-component ESR spectra of the 14-position spin labels demonstrate the coexistence first of gel (L(beta)) and liquid-ordered (L(o)) phases and then of liquid-ordered and liquid-disordered (L(alpha)) phases, with progressively increasing temperature. These phase coexistences are detected over a limited range of cholesterol contents. ESR spectra of the 5-position spin labels register an abrupt increase in ordering at the L(alpha)-L(o) transition and a biphasic response at the L(beta)-L(o) transition. Differences in outer splitting between the C14-labeled sphingomyelin and phosphatidylcholine probes are attributed to partial interdigitation of the sphingomyelin N-acyl chains across the bilayer plane in the L(o) state. In the region where the two fluid phases, L(alpha) and L(o), coexist, the rate at which lipids exchange between phases (<<7 x 10(7) s(-)(1)) is much slower than translational rates in the L(alpha) phase, which facilitates resolution of two-component spectra. |
| Domains of apolipoprotein E contributing to triglyceride and cholesterol homeostasis in vivo. Carboxyl-terminal region 203-299 promotes hepatic very low density lipoprotein-triglyceride secretion Kypreos, K. E., K. W. van Dijk, et al. (2001), J Biol Chem 276(23): 19778-86. Abstract: Apolipoprotein (apo) E has been implicated in cholesterol and triglyceride homeostasis in humans. At physiological concentration apoE promotes efficient clearance of apoE-containing lipoprotein remnants. However, high apoE plasma levels correlate with high plasma triglyceride levels. We have used adenovirus-mediated gene transfer in apoE-deficient mice (E(-)/-) to define the domains of apoE required for cholesterol and triglyceride homeostasis in vivo. A dose of 2 x 10(9) plaque-forming units of apoE4-expressing adenovirus reduced slightly the cholesterol levels of E(-)/- mice and resulted in severe hypertriglyceridemia, due to accumulation of cholesterol and triglyceride-rich very low density lipoprotein particles in plasma. In contrast, the truncated form apoE4-202 resulted in a 90% reduction in the plasma cholesterol levels but did not alter plasma triglyceride levels in the E(-)/- mice. ApoE secretion by cell cultures, as well as the steady-state hepatic mRNA levels in individual mice expressing apoE4 or apoE4-202, were similar. In contrast, very low density lipoprotein-triglyceride secretion in mice expressing apoE4, but not apoE4-202, was increased 10-fold, as compared with mice infected with a control adenovirus. The findings suggest that the amino-terminal 1-202 region of apoE4 contains the domains required for the in vivo clearance of lipoprotein remnants. Furthermore, the carboxyl-terminal 203-299 residues of apoE promote hepatic very low density lipoprotein-triglyceride secretion and contribute to apoE-induced hypertriglyceridemia. |
| Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains Roy, S., R. Luetterforst, et al. (1999), Nat Cell Biol 1(2): 98-105. Abstract: The plasma membrane pits known as caveolae have been implicated both in cholesterol homeostasis and in signal transduction. CavDGV and CavKSY, two dominant-negative amino-terminal truncation mutants of caveolin, the major structural protein of caveolae, significantly inhibited caveola-mediated SV40 infection, and were assayed for effects on Ras function. We find that CavDGV completely blocked Raf activation mediated by H-Ras, but not that mediated by K-Ras. Strikingly, the inhibitory effect of CavDGV on H-Ras signalling was completely reversed by replenishing cell membranes with cholesterol and was mimicked by cyclodextrin treatment, which depletes membrane cholesterol. These results provide a crucial link between the cholesterol-trafficking role of caveolin and its postulated role in signal transduction through cholesterol-rich surface domains. They also provide direct evidence that H-Ras and K-Ras, which are targeted to the plasma membrane by different carboxy-terminal anchors, operate in functionally distinct microdomains of the plasma membrane. |
| Donor splice-site mutation (210+1G_C) in the ApoB gene causes a very low level of ApoB-100 and LDL cholesterol Welty, F. K., K. A. Guida, et al. (2001), Arterioscler Thromb Vasc Biol 21(11): 1864-5. |
| Dose response to a dietary oat bran fraction in cholesterol-fed rats Shinnick, F. L., S. L. Ink, et al. (1990), J Nutr 120(6): 561-8. Abstract: The two objectives of this research were to improve the cholesterol-fed rat as a model for evaluating the hypocholesterolemic potential of foods and to determine the relationship between serum and liver lipid levels in the cholesterol-fed rat and the ingestion of nine levels of a high fiber oat flour (HFOF) derived from oat bran. Ingestion of 0.2% cholic acid, sodium cholate or sodium taurocholate with 1% cholesterol (CH) significantly elevated serum and liver CH, liver triglycerides and liver weight compared to those values in control rats fed diets not containing CH and bile acids; 0.05 and 0.1% cholic acid with 1% CH were also effective. Ingestion of increasing amounts of HFOF, containing 0-10% dietary fiber, by rats made hypercholesterolemic with 1% CH and 0.1% cholic acid in the diet produced a significant inverse relationship between serum and liver cholesterol levels and HFOF intake; r = 0.48, p less than 0.0001 for serum CH and r = 0.55, p less than 0.0001 for liver CH. Because of the similarities in the responses of humans and of the cholesterol-fed rat to oat fiber ingestion, this dose-response relationship in the rat model suggests that larger intakes of soluble oat fiber sources may be accompanied by greater reduction in serum CH levels in humans. |
| Dose-dependent action of atorvastatin in type IIB hyperlipidemia: preferential and progressive reduction of atherogenic apoB-containing lipoprotein subclasses (VLDL-2, IDL, small dense LDL) and stimulation of cellular cholesterol efflux Guerin, M., P. Egger, et al. (2002), Atherosclerosis 163(2): 287-96. Abstract: Type IIB hyperlipidemia is associated with premature vascular disease, an atherogenic lipoprotein phenotype characterised by elevated levels of triglyceride-rich VLDL and small dense LDL, together with subnormal levels of HDL. The dose-dependent and independent effects of a potent HMGCoA reductase inhibitor, Atorvastatin, at daily doses of 10 and 40 mg, were evaluated on triglyceride-rich lipoprotein subclasses (VLDL-1, VLDL-2 and IDL), on the major LDL subclasses (light LDL, LDL-1+LDL-2, D: 1.019-1.029 g/ml; intermediate LDL, LDL-3, D: 1.029-1.039 g/ml and small dense LDL, LDL-4+LDL+5, D: 1.039-1.063 g/ml), on CETP-mediated cholesteryl ester transfer from HDL to apoB-containing lipoproteins, on phospholipid transfer protein activity and on plasma-mediated cellular cholesterol efflux in patients (n=10) displaying type IIB hyperlipidemia. Plasma concentrations of triglyceride-rich lipoprotein subclasses (TRL: VLDL-1, Sf 60-400; VLDL-2, Sf 20-60 and IDL, Sf 12-20) and of LDL (D: 1.019-1.063 g/ml) were markedly diminished after 6 weeks of statin treatment at 10 mg per day (-31 and -36%, respectively; P<0.002) and by 42 and 51%, respectively at the 40 mg per day dose. Increasing doses of atorvastatin progressively normalised both the quantitative and qualitative features of the LDL subclass profile, in which dense LDL predominated at baseline. Indeed, dense LDL levels were reduced by up to 57% at the 40-mg dose, leading to a shift in the peak of the density profile towards larger, buoyant LDL particles typical of normolipidemic subjects. In addition, marked reduction in numbers of apoB100-containing particle acceptors led to a 30% decrease (P<0.02) in CETP-mediated CE transfer from HDL. Finally, a significant dose-dependent statin-mediated elevation (+15% at 10 mg; P=0.0003 and +35% at 40 mg; P<0.0001 compared to baseline) in the capacity of plasma from type IIB subjects to mediate free cholesterol efflux from Fu5AH hepatoma cells was observed. Moreover, atorvastatin (40 mg per day) significantly increased plasma apoAI levels (+24%; P<0.05), thereby suggesting that this statin enhances production of apoAI and with it, formation of nascent pre-beta HDL particles. Plasma PLTP activity was not affected by either dose of atorvastatin. We conclude that increasing the dose of atorvastatin leads to dose-dependent, preferential and progressive reduction in particle numbers of atherogenic VLDL-2, IDL and dense LDL, and concomitantly, to enhanced cellular cholesterol efflux in type IIB dyslipidemia, thereby diminishing the atherosclerotic burden in subjects characterised by high cardiovascular risk. |
| Dose-dependent effect of hydroxymethylglutaryl-coenzyme A reductase inhibitor on serum cholesterol with limited dietary restrictions: a case study Okada, S., K. Ichiki, et al. (1993), J Int Med Res 21(2): 105-11. Abstract: Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (pravastatin sodium) can selectively inhibit cholesterol biosynthesis in the liver and may lower serum cholesterol concentrations even where there are no particular dietary restrictions. A 72-year old housewife with non-insulin-dependent diabetes mellitus complicated by hyperlipaemia type IIb, who did not follow directions for diet therapy or kinesitherapy, was administered HMG-CoA reductase inhibitor. The initial dose of 10 mg/day HMG-CoA reductase inhibitor was increased by 10 mg/day every 4 weeks to 30 mg/day, maintained at 30 mg/day for 8 weeks and then reduced gradually until discontinuation after a further 27 weeks. Test results showed the changes in low-density lipoprotein cholesterol and apoprotein B to be dose-dependent. The findings represent the first clinical evidence that hypercholesterolaemia can be adequately managed by the use of HMG-CoA reductase inhibitor, even when no specific dietary restrictions are imposed, and may contribute to improvements in the quality of daily life for many patients suffering from hyperlipaemia type IIb. |
| Dose-dependent effect on serum cholesterol and apoprotein B concentrations by consumption of boiled, non-filtered coffee Aro, A., J. Teirila, et al. (1990), Atherosclerosis 83(2-3): 257-61. Abstract: The effects of boiled coffee (BC) and filtered coffee (FC) on serum lipoproteins were compared in 41 healthy subjects whose serum cholesterol concentration was less than 7 mmol/l. The subjects consumed in random order BC and FC for 4-week periods in a crossover design. The individual daily consumption ranged from 2 to 14 cups (mean 5.7 cups per day) and was similar during both study periods. The serum total and LDL-cholesterol and apoprotein B concentrations were higher (P less than 0.001) and HDL-cholesterol lower (P less than 0.05) after BC than after FC. Bodyweight, apoprotein A-I and triglycerides remained unchanged. In the 16 subjects who consumed coffee less than 5 cups per day the difference in serum total cholesterol between the BC and FC periods was non-significant (P = 0.16). The differences in serum total cholesterol and LDL-cholesterol between the periods showed significant linear correlations with the amount of coffee consumed daily (r = 0.52, P less than 0.001 and r = 0.33, P less than 0.05, respectively) but no association was found between the difference in HDL-cholesterol and the amount of coffee (r = 0.14, P = 0.39). The results indicate a dose-dependent increasing effect on serum total and LDL-cholesterol and apoprotein B concentrations of boiled coffee. |
| Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives Martinez-Botas, J., A. J. Ferruelo, et al. (2001), Biochim Biophys Acta 1532(3): 185-94. Abstract: The mevalonate pathway is tightly linked to cell proliferation. The aim of the present study is to determine the relationship between the inhibition of this pathway by lovastatin and the cell cycle. HL-60 and MOLT-4 human cell lines were cultured in a cholesterol-free medium and treated with increasing concentrations of lovastatin, and their effects on cell proliferation and the cell cycle were analyzed. Lovastatin was much more efficient in inhibiting cholesterol biosynthesis than protein prenylation. As a result of this, lovastatin blocked cell proliferation at any concentration used, but its effects on cell cycle distribution varied. At relatively low lovastatin concentrations (less than 10 microM), cells accumulated preferentially in G(2) phase, an effect which was both prevented and reversed by low-density lipoprotein cholesterol. At higher concentrations (50 microM), the cell cycle was also arrested at G(1) phase. In cells treated with lovastatin, those arrested at G(1) progressed through S upon mevalonate provision, whereas cholesterol supply allowed cells arrested at G(2) to traverse M phase. These results demonstrate the distinct roles of mevalonate, or its non-sterol derivatives, and cholesterol in cell cycle progression, both being required for normal cell cycling. |
| Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans Qureshi, A. A., S. A. Sami, et al. (2002), Atherosclerosis 161(1): 199-207. Abstract: Tocotrienols are effective in lowering serum total and LDL-cholesterol levels by inhibiting the hepatic enzymic activity of beta-hydroxy-beta-methylglutaryl coenzymeA (HMG-CoA) reductase through the post-transcriptional mechanism. alpha-Tocopherol, however, has an opposite effect (induces) on this enzyme activity. Since tocotrienols are also converted to tocopherols in vivo, it is necessary not to exceed a certain dose, as this would be counter-productive. The present study demonstrates the effects of various doses of a tocotrienol-rich fraction (TRF25) of stabilized and heated rice bran in hypercholesterolemic human subjects on serum lipid parameters. Ninety (18/group) hypercholesterolemic human subjects participated in this study, which comprised three phases of 35 days each. The subjects were initially placed on the American Heart Association (AHA) Step-1 diet and the effects noted. They were then administered 25, 50, 100, and 200 mg/day of TRF25 while on the restricted (AHA) diet. The results show that a dose of 100 mg/day of TRF25 produce maximum decreases of 20, 25, 14 (P<0.05) and 12%, respectively, in serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides compared with the baseline values, suggesting that a dose of 100 mg/day TRF25 plus AHA Step-1 diet may be the optimal dose for controlling the risk of coronary heart disease in hypercholesterolemic human subjects. |