| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Amount of cholesterol in foods Itakura, H. (2001), Nippon Rinsho 59 Suppl 3: 555-8. |
| Amperometric cholesterol biosensor based on in situ reconstituted cholesterol oxidase on an immobilized monolayer of flavin adenine dinucleotide cofactor Vidal, J. C., J. Espuelas, et al. (2004), Anal Biochem 333(1): 88-98. Abstract: A new amperometric biosensor for determining cholesterol based on deflavination of the enzyme cholesterol oxidase (ChOx) and subsequent reconstitution of the apo-protein with a complexed flavin adenine dinucleotide (FAD) monolayer is described. The charge transfer mediator pyrroquinoline quinone (PQQ) was covalently bound to a cystamine self-assembled monolayer (SAM) on an Au electrode. Boronic acid (BA) was then bound to PQQ using the carbodiimide procedure, and the BA ligand was complexed to the FAD molecules on which the apo-ChOx was subsequently reconstituted. The effective release of the FAD from the enzyme and the successful reconstitution were verified using molecular fluorescence and cyclic voltammetry. The optimal orientation of FAD toward the PQQ mediator and the distances between FAD and PQQ and between PQQ and electrode enhance the charge transfer, very high sensitivity (about 2,500 nAmM(-1)cm(-2)) being obtained for cholesterol determination. The biosensor is selective toward electroactive interferents (ascorbic acid and uric acid) and was tested in reference serum samples, demonstrating excellent accuracy (relative errors below 3% in all cases). The biosensor activity can be successfully regenerated in a simple process by successive reconstitution with batches of recently prepared apo-ChOx on the same immobilized Au/SAM-PQQ-BA-FAD monolayer (it was tested five times); the lifetime of the biosensor is about 45-60 days. |
| Amperometric determination of high-density lipoprotein cholesterol using polyethylene glycol-modified enzymes and a peroxidase-entrapped electrode Kinoshita, H., M. Torimura, et al. (1998), Ann Clin Biochem 35 (Pt 6): 739-44. Abstract: A peroxidase-entrapped and ferrocene-embedded carbon paste (POD-Fc-CP) electrode allows a highly sensitive detection of H2O2 at levels as low as 10 nmol/L with practically no interference by coexisting substances, turbidity or coloration of samples. The electrode was applied to the amperometric determination of high-density lipoprotein (HDL)-cholesterol in a very small volume (1-2 microL) using polyethylene glycol (PEG)-modified cholesterol esterase and cholesterol oxidase without prior precipitation or separation of HDL. PEG-modified enzymes exhibit a selective activity toward HDL-cholesterol in the presence of dextran sulphate and MgCl2 to generate H2O2. The HDL-cholesterol concentrations of human serum samples determined by this method showed a good correlation with those determined by an ordinary spectrophotometric method using PEG-modified enzymes and peroxidase or by a conventional precipitation method. |
| Amperometric determination of total cholesterol at gold electrodes covalently modified with cholesterol oxidase and cholesterol esterase with use of thionin as an electron mediator Nakaminami, T., S. Ito, et al. (1999), Anal Chem 71(5): 1068-76. Abstract: Immobilization of cholesterol oxidase (EC 1.1.3.6) (ChOx) on a gold electrode was attempted by cross-linking using glutaraldehyde between ChOx molecules and a self-assembled monolayer of 2-aminoethanethiolate. The resulting electrode (ChOx/Au) exhibits an amperometric response to free cholesterol in the presence of thionin as an electron mediator, and a steady-state response is obtained approximately 60 s after injection of cholesterol into the electrolyte solution. Coimmobilization of cholesterol esterase (EC 3.1.1.13) (ChE) and ChOx (ChE/ChOx/Au) allows the amperometric determination of both esterified cholesterol and free cholesterol. Cyclic voltammetry of the ChE/ChOx/Au and the dependence of the amperometric response to cholesterol on the concentration of thionin suggest that thionin is encapsulated in the enzyme film on the electrode surface. Apparent Michaelis constants of the ChOx/Au and the ChE/ChOx/Au electrodes suggest that the amperometric response was controlled by penetration of the reaction substrate into the films of the enzyme(s). The concentration of total (free and esterified) cholesterol in human serum samples, determined by using the techniques developed in the present study, is in good agreement with that determined by the well-established technique using colorimetry. |
| Amphiphilic block copolymers as bile acid sorbents: 2. Polystyrene-b-poly(N,N,N-trimethylammoniumethylene acrylamide chloride): self-assembly and application to serum cholesterol reduction Cameron, N. S., A. Eisenberg, et al. (2002), Biomacromolecules 3(1): 124-32. Abstract: This paper presents morphological studies and preliminary bile salt binding properties of the new amphiphilic diblock copolymer polystyrene-b-poly(N,N,N-trimethylammoniumethylene acrylamide chloride) (PS-b-PTMEACl)(1) (see Figure 1), a derivative of PS-b-poly(tert-butylacrylate) (PS-b-PtBuA). In an aqueous environment, PS-b-PTMEACl forms simple spheres (approximately 20 nm diameter), large compound micelles (>100 nm diameter), and larger, more complex architectures as presented and discussed below. The colloidal stability with respect to sodium chloride and as a function of particle concentration is also considered. Finally, PS-b-PTMEACl aggregates were prepared and tested as an alternative to the commercially available bile salt sequestrant resins that target coronary heart disease due to elevated cholesterol levels. Electron micrographs were employed to visualize the colloid-based polyelectrolyteminus signbiosurfactant interaction and chromatographic separation analytical methods were used to quantify the sequestration. The results indicate that although at this preliminary stage they require laborious preparation, self-assembled aggregates may present an interesting alternative to the clinically used bile salt sequestrants. |
| Amphotericin B lipid complex or amphotericin B multiple-dose administration to rabbits with elevated plasma cholesterol levels: pharmacokinetics in plasma and blood, plasma lipoprotein levels, distribution in tissues, and renal toxicities Ramaswamy, M., K. D. Peteherych, et al. (2001), Antimicrob Agents Chemother 45(4): 1184-91. Abstract: The purpose of the present study was to determine if a relationship exists between the plasma cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the pharmacokinetics of AmpB in plasma in hypercholesterolemic rabbits administered multiple doses of amphotericin B (AmB) deoxycholate (Doc-AmB) and AmB lipid complex (ABLC). After 7 days of administration of a cholesterol-enriched diet (0.50% wt/vol) or a regular rabbit diet, each rabbit was administered a single intravenous bolus of Doc-AmB (n = 8) or ABLC (n = 10) (1.0 mg/kg of body weight) daily for 7 consecutive days (a total of eight doses). Blood samples were obtained daily before and 24 h after the administration of each dose and serially thereafter following the administration of the last dose for the assessment of pharmacokinetics in plasma, kidney toxicity, plasma lipoprotein levels, and drug distribution in tissue. The pharmacokinetics of AmB in blood following the administration of ABLC were also determined in rabbits fed cholesterol-enriched and regular diets (n = 3 each group). Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total, low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) cholesterol levels in plasma compared with the levels in rabbits on a regular diet. No significant differences in total plasma triglyceride levels were observed. Significant increases in plasma creatinine levels were observed in rabbits fed a cholesterol-enriched diet (P < 0.05) and rabbits fed a regular diet (P < 0.05) when administered AmB. However, the magnitude of this increase was twofold greater in rabbits fed a regular diet than in rabbits fed a cholesterol-enriched diet. An increase in plasma creatinine levels was observed only in rabbits on a cholesterol-enriched diet administered ABLC. The pharmacokinetics of AmB were significantly altered in rabbits on a cholesterol-enriched diet administered Doc-AmB or ABLC compared to those in rabbits on a regular diet administered each of these compounds. The pharmacokinetics of AmB in blood were significantly different following ABLC administration but not following Doc-AmB administration in both rabbits fed cholesterol-enriched diets and rabbits fed regular diets compared to their corresponding pharmacokinetics in plasma. An increased percentage of AmB was recovered in the TRL fraction when Doc-AmB was administered to rabbits fed a cholesterol-enriched diet than when it was administered to rabbits fed a regular diet. Furthermore, an increased percentage of AmB was recovered in the LDL and TRL fractions when ABLC was administered to rabbits fed a cholesterol-enriched diet rabbits fed a regular diet. These findings suggest that an increase in plasma cholesterol levels modifies the pharmacokinetics of AmB and renal toxicity following the administration of multiple intravenous doses of Doc-AmB and ABLC. |
| Amyloid beta peptide alters intracellular vesicle trafficking and cholesterol homeostasis Liu, Y., D. A. Peterson, et al. (1998), Proc Natl Acad Sci U S A 95(22): 13266-71. Abstract: Amyloid beta peptide (Abeta) is thought to play a central role in the pathogenesis of Alzheimer disease (AD). How Abeta induces neurodegeneration in AD is not known. A connection between AD and cholesterol metabolism is suggested by the finding that people with the apolipoprotein E4 allele, a locus coding for a cholesterol-transporting lipoprotein, have a modified risk for both late-onset AD and cardiovascular disease. In the present study we show that both Abeta and submicromolar concentrations of free cholesterol alter the trafficking of a population of intracellular vesicles that are involved in the transport of the reduced form of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT formazan), the formation of which is a widely used cell viability assay. Treatments that change cellular free cholesterol levels also modulate the trafficking of the MTT formazan-containing vesicles, suggesting that the trafficking of these vesicles may be regulated by free cholesterol under physiological conditions. In addition, Abeta decreases cholesterol esterification and changes the distribution of free cholesterol in neurons. These results suggest that the MTT formazan-transporting vesicles may be involved in cellular cholesterol homeostasis and that the alteration of vesicle transport by Abeta may be relevant to the chronic neurodegeneration observed in AD. |
| Amyloid beta-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region Chochina, S. V., N. A. Avdulov, et al. (2001), J Lipid Res 42(8): 1292-7. Abstract: There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid beta-peptide may play an important role in this interaction. Abeta destabilizes brain membranes and this action of Abeta may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Abeta1-40 on the annular fluidity (i.e., lipid environment adjacent to proteins) and bulk fluidity of rat synaptic plasma membranes (SPM) of the cerebral cortex, cerebellum, and hippocampus using the fluorescent probe pyrene and energy transfer. Amounts of cholesterol and phospholipid of SPM from each brain region were determined. SPM of the cerebellum were significantly more fluid as compared with SPM of the cerebral cortex and hippocampus. Abeta significantly increased (P < or = 0.01) annular and bulk fluidity in SPM of cerebral cortex and hippocampus. In contrast, Abeta had no effect on annular fluidity and bulk fluidity of SPM of cerebellum. The amounts of cholesterol in SPM of cerebral cortex and hippocampus were significantly higher (P < or = 0.05) than amount of cholesterol in SPM of cerebellum. There was significantly less (P < or = 0.05) total phospholipid in cerebellar SPM as compared with SPM of cerebral cortex. Neuronal membranes enriched in cholesterol may promote accumulation of Abeta by hydrophobic interaction, and such an interpretation is consistent with recent studies showing that soluble Abeta can act as a seed for fibrillogenesis in the presence of cholesterol. |
| Amyloid beta-protein affects cholesterol metabolism in cultured neurons: implications for pivotal role of cholesterol in the amyloid cascade Gong, J. S., N. Sawamura, et al. (2002), J Neurosci Res 70(3): 438-46. Abstract: Recently, we have found that alterations in cellular cholesterol metabolism are involved in promotion of tau phosphorylation (Fan et al. 2001 J. Neurochem. 76: 391-400; Sawamura et al. 2001 J. Biol. Chem. 276:10314-10319). In addition, we have shown that amyloid beta-protein (A beta) promotes cholesterol release to form A beta-lipid particles (Michikawa et al. 2001 J. Neurosci. 21:7226-7235). These lines of evidence inspired us to conduct further studies on whether A beta affects cholesterol metabolism in neurons, which might lead to tau phosphorylation. Here, we report the effect of A beta1-40 on cholesterol metabolism in cultured neurons prepared from rat cerebral cortex. Oligomeric A beta1-40 inhibited cholesterol synthesis and reduced cellular cholesterol levels in a dose- and time-dependent manner, while freshly dissolved A beta had no effect on cholesterol metabolism. However, oligomeric A beta had no effect on the proteolysis of sterol regulatory element binding protein-2 (SREBP-2) or protein synthesis in cultured neurons. Oligomeric A beta did not enhance lactate dehydrogenase (LDH) release from neuronal cells or decrease signals in the cultures reactive to 3,3'-BisN,N-bis(carboxymethyl)aminomethylfluorescein, hexaacetoxymethyl ester (calcein AM) staining, indicating that A beta used in this experiment did not cause neuronal death during the time course of our experiments. Since alterations in cholesterol metabolism induce tau phosphorylation, our findings that oligomeric A beta alters cellular cholesterol homeostasis may provide new insight into the mechanism underlying the amyloid cascade hypothesis. |
| Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alzheimer's disease Gibson Wood, W., G. P. Eckert, et al. (2003), Biochim Biophys Acta 1610(2): 281-90. Abstract: Amyloid beta-protein (Abeta) is thought to be one of the primary factors causing neurodegeneration in Alzheimer's disease (AD). This protein is an amphipathic molecule that perturbs membranes, binds lipids and alters cell function. Several studies have reported that Abeta alters membrane fluidity but the direction of this effect has not been consistently observed and explanations for this lack of consistency are proposed. Cholesterol is a key component of membranes and cholesterol interacts with Abeta in a reciprocal manner. Abeta impacts on cholesterol homeostasis and modification of cholesterol levels alters Abeta expression. In addition, certain cholesterol lowering drugs (statins) appear to reduce the risk of AD in human subjects. However, the role of changes in the total amount of brain cholesterol in AD and the mechanisms of action of statins in lowering the risk of AD are unclear. Here we discuss data on membranes, cholesterol, Abeta and AD, and propose that modification of the transbilayer distribution of cholesterol in contrast to a change in the total amount of cholesterol provides a cooperative environment for Abeta synthesis and accumulation in membranes leading to cell dysfunction including disruption in cholesterol homeostasis. |
| Amyloid precursor protein in unique cholesterol-rich microdomains different from caveolae-like domains Hayashi, H., T. Mizuno, et al. (2000), Biochim Biophys Acta 1483(1): 81-90. Abstract: To determine the localization of the amyloid precursor protein (APP) on the cellular membrane, we performed membrane fractionation of cultured cells including that of Madin-Darby canine kidney (MDCK) and P19 cells transfected with human APP cDNA, non-transfected SH-SY5Y cells, and rat cerebral cortices. In MDCK cells, APP was exclusively present in abundance in the supernatant following solubilization of the plasma membranes using Triton X-100, and in high-density fractions of sucrose density gradient fractionation (SDGF) following Triton X-100 solubilization of whole cellular membranes. Caveolin-1 was not cofractionated with APP. In experiments using P19 cells and rat cerebral cortices, we detected two isoforms of APP. The APP with the apparently lower molecular weight (immature type) coexisted in abundance with integrin in the high-density fractions, whereas the APP with the apparently higher molecular weight (mature type) was recovered predominantly in the low-density fractions with cholesterol and GM1 gangliosides, the concentrations of which were higher than those in the bulk plasma membranes, but lower than those in caveolae-like domains (CLDs), following SDGF of Triton X-100-solubilized cellular membranes. The results of this study suggest the following; first, APP is not present in abundance in caveolae or CLDs, but is in unique cholesterol-rich microdomains; second, the targeting of APP to these unique microdomains may be linked to the maturation of APP in some cells. |
| An abnormal cholesterol profile in young adults with normocholesterolemic cerebral ischemia Chen, W. H., M. Y. Lan, et al. (2000), Kaohsiung J Med Sci 16(3): 141-7. Abstract: An abnormal cholesterol fraction can still be able to provoke cascades of lipidic atherogenesis even when the serum TC level is within normal range (< 200 mg%). However, there is a shortage of convincing data concerning cerebral atherogenesis in young Asians who have a different diet habit and living style from those in western countries. In this study, we examined the lipoprotein-cholesterol profile in young Taiwanese patients with noncardiac cerebral ischemia (NCCI) whose serum TC level was < 200 mg% and 200-250 mg%. The results showed a decrease of HDLC and an increase of VLDLC in patients with TC < 200 mg%, but only a decrease of HDLC in patients with TC = 200-250 mg%. The cholesterol fraction metabolism is obviously perplexed in NCCI subjects. These findings were not related to their associated risk factors. Accordingly, a derangement of cholesterol fraction with normal serum TC level can also incite lipidic cerebral atherogenesis in young Taiwanese adults. Therefore, a detailed evaluation of cholesterol profile should be born in mind in young eastern NCCI patients despite of a normal serum TC level. Tailored measure of diet and living should be modified to prevent lipidic atherogenesis in our society in future. |
| An acetylation method for the quantification of membrane lipids, including phospholipids, polyphosphoinositides and cholesterol Stein, J. M., G. A. Smith, et al. (1991), Biochem J 274 (Pt 2): 375-9. Abstract: A method for the quantification of membrane lipids by acetylation with 3Hacetic anhydride is described. A standard lipid, labelled with 14C or 32P, is added to the sample and is simultaneously acetylated. The 3H/14C or 3H/32P ratios obtained in the acetylated lipids are proportional to the initial lipid concentration. The method has been used to quantify cholesterol, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in amounts between 2 and 10 nmol. |
| An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat astrocytes Ueno, S., J. Ito, et al. (2002), Biochim Biophys Acta 1589(3): 261-72. Abstract: Production and release of apolipoprotein (apo) E and cholesterol were highly upregulated in the astrocytes prepared by 1-week secondary culture after 1-month primary culture of rat fetal brain cells (M/W cells) in comparison to the cells prepared by a conventional method of 1-week primary and 1-week secondary culture (W/W cells). Both cell preparations were mostly composed of astrocytes with small population of other glial cells, except that type-2 astrocyte-like cells accounted for 5-15% of M/W cells indicating more activated and/or matured status. The conditioned medium of the 1-month primary culture stimulated W/W cells to increase the release of apoE and cholesterol into the medium. The treatment of W/W cells by acidic fibroblast growth factor (aFGF) similarly upregulated biosyntheses and release of apoE and cholesterol. The effect of the conditioned medium was completely inhibited by pretreatment with an anti-aFGF antibody. The increase of the aFGF message was demonstrated in the brain cells after 1-month primary culture. The findings suggested that an aFGF-like trophic factor upregulates biosynthesis and secretion of apoE-high density lipoprotein (HDL) in astrocytes probably by autocrine stimulation in this culture system. Since this cytokine is highly expressed in the development or post-injury period of the brain, it putatively activates intercellular cholesterol transport to support construction or recovery of the brain. |
| An alternative mechanism for the inhibition of cholesterol biosynthesis in HepG2 cells by N-(1,5,9)-trimethyldecyl-4 alpha,10-dimethyl-8-aza-trans-decal-3 beta-ol (MDL 28,815) Van Sickle, W. A., P. K. Wilson, et al. (1993), J Pharmacol Exp Ther 267(3): 1243-9. Abstract: Compounds that block hepatic cholesterol biosynthesis and secretion may be useful hypocholesterolemic agents. N-(1,5,9)-trimethyldecyl-4 alpha,10-dimethyl-8-aza-trans-decal-3 beta-ol (MDL 28,815) has been shown to block cholesterol biosynthesis in 3T3 fibroblasts and it causes cellular accumulation of squalene 2,3-epoxide and squalene 2,3:23,24-diepoxide (squalene epoxides), which suggests that it inhibits 2,3-oxidosqualene cyclase. The purpose of the present report was to determine whether MDL 28,815 acts only at the level of 2,3-oxidosqualene cyclase or whether other enzymes in the cholesterol biosynthetic pathway are affected. HepG2 cells, grown in lipoprotein-deficient serum, were incubated with MDL 28,815 and 14C-acetate to radiolabel cholesterol and the intermediates in the cholesterol biosynthetic pathway. Blockade of cholesterol biosynthesis by MDL 28,815 in these cells was associated with the accumulation of two metabolites, one of which was 5 alpha-cholest-8-en-3 beta-ol. The other metabolite was identified by a combination of ultraviolet spectrometry, gas chromatography, mass spectroscopy and analytical high-performance liquid chromatography as 5 alpha-cholest-8,14-dien-3 beta-ol. Maximal blockade of cholesterol biosynthesis was associated with the accumulation of these two metabolites and, in particular, 5 alpha-cholest-8,14-dien-3 beta-ol, rather than with squalene epoxides. These results suggest that MDL 28,815 blocks cholesterol biosynthesis primarily by the inhibition of sterol-delta 14-reductase, and possibly sterol-delta 8-ene isomerase, rather than 2,3-oxidosqualene cyclase. |
| An amperometric cholesterol biosensor based on multiwalled carbon nanotubes and organically modified sol-gel/chitosan hybrid composite film Tan, X., M. Li, et al. (2005), Anal Biochem 337(1): 111-20. Abstract: A new type of amperometric cholesterol biosensor based on sol-gel chitosan/silica and multiwalled carbon nanotubes (MWCNTs) organic-inorganic hybrid composite material was developed. The hybrid composite film was used to immobilize cholesterol oxidase on the surface of Prussian blue-modified glass carbon electrode. Effects of some experimental variables such as enzyme loading, concentration of Triton X-100, pH, temperature, and applied potential on the current response of the biosensor were investigated. Analytical characteristics and dynamic parameters of the biosensors with and without MWCNTs in the hybrid film were compared, and the results show that analytical performance of the biosensor can be improved greatly after introduction of the MWCNTs. Response time, sensitivity, linear range, limit of detection (S/N=3), and apparent Michaelis-Menten constant Km are 25s, 0.54 microA mM(-1), 8.0 x 10(-6) to 4.5 x 10(-4) M, 4.0 x 10(-6) M, and 0.41 mM for the biosensor without MWCNTs and 13 s, 1.55 microA mM(-1), 4.0 x 10(-6) to 7.0 x 10(-4) M, 1.0 x 10(-6) M, and 0.24 mM for the biosensor with MWCNTs, respectively. The activation energy of the enzyme-catalyzed reaction was measured to be 42.6 kJ mol(-1). This method has been used to determine the free cholesterol concentration in real human blood samples. |
| An analysis of cholesterol control and statin use in the Losartan Intervention for Endpoint Reduction in Hypertension Study Kristianson, K., F. Fyhrquist, et al. (2003), Clin Ther 25(4): 1186-99. Abstract: BACKGROUND: There is general agreement that patients who have elevated lipid levels and/or risk factors for or existing cardiovascular disease should receive aggressive cholesterol-lowering therapy. However, it is not clear whether patients are receiving the recommended treatment. OBJECTIVE: This study evaluated cholesterol control and statin use in the setting of a large, long-term cardiovascular end point trial. METHODS: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study was conducted between 1995 and 2001 to compare the incidence of cardiovascular morbidity and mortality with losartan- or atenolol-based treatment in 9193 patients aged 55 to 80 years with hypertension and left ventricular hypertrophy. The mean (SD) duration of follow-up was 4.8 (0.9) years. Use of lipid-lowering therapy was at the discretion of the investigator. In the present study, analyses of baseline and end-of-study mean total cholesterol (TC) and high-density lipoprotein cholesterol levels and statin use were performed for the combined treatment groups. Based on generally accepted guidelines, achievement of a TC level <5.0 mmol/L (193.5 mg/dL) was used as the treatment target for the purpose of these analyses. The proportions of patients with TC levels above this cutoff were calculated at baseline and at the final visit. RESULTS: A total of 8653 patients had baseline and end-of-study cholesterol measurements and were included in this analysis. At baseline, 528 (6.1%) patients were receiving statins; TC levels were above the cutoff in 381 (72.2%) of these patients, who had a mean TC level of 6.07 mmol/L (234.7 mg/dL). Of 8125 (93.9%) patients who were not receiving statins at baseline, TC levels were above the cutoff in 6859 (84.4%), with a mean TC level of 6.37 mmol/L (246.4 mg/dL). At the end of the study, 1892 (21.9%) patients were receiving a statin; TC levels were above the cutoff in 1096 (57.9%) of these patients, who had a mean TC level of 5.99 mmol/: (231.6 mg/dL). Of 6761 (78.1%) patients who were not receiving statins at the end of the study, TC levels were above the cutoff in 5316 (78.6%), with a mean TC level of 6.24 mmol/L (241.4 mg/dL). CONCLUSIONS: In this long-term cardiovascular end point study in patients with moderate to severe hypertension and left ventricular hypertrophy, statins were not optimally administered and cholesterol levels were poorly controlled. |
| An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence Holme, I. (1990), Circulation 82(6): 1916-24. Abstract: The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease (CHD) incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored. All randomized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence; analysis was performed with weighted linear regression. The trials include those that used primary and secondary intervention, diet and drugs, and single or multifactor design. Nineteen trials were analyzed for total mortality, and of the 19, 16 were analyzed for CHD incidence rate. Net difference in cholesterol change between study groups was used as the independent variable, and the three previously mentioned dichotomous design characteristics were used as additional independent variables. For every 1% reduction in cholesterol, an estimated 2.5% reduction in CHD incidence is indicated (95% CL: 1.1, 3.9). With regard to CHD drug trials tended toward better efficiency in cholesterol lowering than did dietary trials. With regard to total mortality, this efficiency was higher in secondary than in primary preventive trials. The efficiency was also somewhat dependent on the baseline cholesterol level. This study shows that cholesterol reduction is effective in lowering CHD incidence, but cholesterol reduction must be at least 8-9% to be effective in lowering total mortality. |
| An angiotensin converting enzyme inhibitor, perindopril, prevents progression of preformed atherosclerotic lesions in the cholesterol-fed rabbit Fennessy, P. A., J. H. Campbell, et al. (1994), Clin Sci (Lond) 87(6): 685-91. Abstract: 1. The aim was to determine whether the angiotensin converting enzyme inhibitor perindopril, at a concentration approaching that used in human antihypertensive therapy, influences progression of preformed atherosclerotic plaques. 2. Rabbits had their right carotid artery deendothelialized with a balloon catheter, which resulted in the formation of a myointimal thickening. 3. At 14 weeks post surgery groups I, II and III (n = 6 per group) were fed a 1% cholesterol-enriched diet for 6 weeks, then group I rabbits were sacrificed. Groups II and III were placed on a normolipidaemic diet for a further 6 weeks with group III rabbits also receiving 0.3 mg day-1 kg-1 perindopril. Groups IV and V were treated the same as groups II and III, respectively, except that they received a normal diet throughout. 4. Group I rabbits fed a 1% cholesterol-enriched diet for 6 weeks developed lipid-filled lesions covering 26.3 +/- 14.3% of the surface area of the descending thoracic aorta. This was exacerbated in rabbits fed a 1% cholesterol diet for 6 weeks followed by 6 weeks on a normal diet (61.2 +/- 27.3%). In rabbits fed a 1% cholesterol diet for 6 weeks than a normal diet for a further 6 weeks plus 0.3 mg day-1 kg-1 perindopril, the percentage surface area covered by lesions was 21.8 +/- 15.8%. No lesions developed in the aortas of rabbits fed a normal diet. In the right coronary artery the resulting neointima in rabbits fed a 1% cholesterol diet for 6 weeks only was 42.4 +/- 5.7% of the cross-sectional area of the vessel wall, 57.4 +/- 8.0% in rabbits receiving 6 weeks' cholesterol diet than 6 weeks' normal diet, 36.0 +/- 6.6% in rabbits fed a 6-week cholesterol diet than 6 weeks' normal diet with 0.3 mg day-1 kg-1 perindopril and 33.2 +/- 4.9% and 31.8 +/- 3.1% in rabbits on a normal diet throughout with 0 and 0.3 mg day-1 kg-1 perindopril respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
| An anti-atherogenic effect of Schistosoma mansoni infections in mice associated with a parasite-induced lowering of blood total cholesterol Doenhoff, M. J., R. G. Stanley, et al. (2002), Parasitology 125(Pt 5): 415-21. Abstract: In affluent societies the prevalences of so-called 'Western' diseases such as atherosclerosis, allergies and autoimmune disorders appear to have increased, while many diseases caused by communicable infections are now relatively less common. To test whether there may be a causal relationship we examined the effects of Schistosoma mansoni infections in mice that develop cardiovascular pathology as a result of a genetic deficiency in apolipoprotein E (apoE-/-). The development of atherosclerotic lesions in the aortic arch and brachiocephalic artery of the apoE-/- mice was reduced by approximately 50% in mice with the parasitic infection, when comparison was made with uninfected control mice fed the same diet. Observations on S. mansoni-infected conventional laboratory mice indicate that patent schistosome infections could be counteracting the effects of an atherogenic diet by modulating host lipid metabolism and inducing a reduction in blood total cholesterol concentrations. |