Cholesterol Journal Articles

Record 11921 to 11940

Stimulation of CTP:phosphocholine cytidylyltransferase by free cholesterol loading of macrophages involves signaling through protein dephosphorylation
Shiratori, Y., M. Houweling, et al. (1995), J Biol Chem 270(50): 29894-903.
Abstract: Free cholesterol-loaded macrophages in atheromata synthesize excess phosphatidylcholine (PC), which may be an important adaptive response to the excess free cholesterol (FC) load. We have recently shown that FC loading of macrophages leads to 2-4-fold increases in PC mass and biosynthesis and to the post-translational activation of the membrane-bound form of CTP:phosphocholine cytidylyltransferase (CT), a key enzyme in PC biosynthesis. Herein, we explore further the mechanism of CT activation in FC-loaded macrophages. First, enrichment of membranes from control macrophages with FC in vitro did not increase CT activity, and PC biosynthesis in vivo is up-regulated by FC loading even when CT and FC appear to be mostly in different intracellular sites. These data imply that FC activates membrane-bound CT by a signaling mechanism. That the proposed signaling mechanism involves structural changes in the CT protein was suggested by data showing that two different antibodies against synthetic CT peptides showed increased recognition of membrane-bound CT from FC-loaded cells despite no increase in CT protein. Since CT is phosphorylated, two-dimensional maps of peptides from 32P-labeled control and FC-loaded macrophages were compared: six peptide spots from membrane-bound CT, but none from soluble CT, were dephosphorylated in the FC-loaded cells. Furthermore, incubation of FC-loaded macrophages with the phosphatase inhibitor, calyculin A, blocked increases in both PC biosynthesis and antipeptide-antibody recognition of CT. Last, treatment of membranes from control macrophages with lambda phage protein phosphatase in vitro increased both CT activity (2-fold) and antipeptide-antibody recognition of CT; soluble CT activity and antibody recognition were not substantially affected by phosphatase treatment. In summary, FC loading of macrophages leads to the partial dephosphorylation of membrane-bound CT, and possibly other cellular proteins, which appears to be important in CT activation. This novel regulatory action of FC may allow macrophages to adapt to FC loading in atheromata.

Stimulation of fatty acid biosynthesis by dietary cholesterol and of cholesterol synthesis by dietary fatty acid
Fungwe, T. V., J. E. Fox, et al. (1994), J Lipid Res 35(2): 311-8.
Abstract: We reported previously that dietary cholesterol produces hypertriglyceridemia in the rat, accompanied by reduced oxidation and increased incorporation of exogenous fatty acid into hepatic triglyceride and increased secretion of very low density lipoprotein. We now report that dietary cholesterol also increases net hepatic fatty acid synthesis and the incorporation of newly synthesized fatty acid into hepatic triglyceride in vivo. Male rats were fed a cholesterol-free, semisynthetic diet (5% w/w corn oil) for 7 days, or the same diet supplemented with 0.5% cholesterol. On the day of the experiments, fed animals received 5 mCi 3H2O intraperitoneally (i.p.) either at 1200 h (6 h into the light cycle) or at 2400 h (6 h into the dark cycle). Animals were killed 1 h after receiving the radioisotope. Feeding cholesterol increased hepatic triglyceride and cholesteryl ester concentrations, moderately elevated the content of free cholesterol, but did not affect phospholipid levels. Increased net synthesis of fatty acids by livers of animals receiving cholesterol was observed during the dark period; a similar increase during the light period was also observed for incorporation of newly synthesized fatty acid into hepatic phospholipid and cholesteryl ester, although incorporation into triglyceride was of borderline significance (P < 0.06). In other experiments male rats were fed similar diets for 3, 7, or 21 days. Fed animals received 10 mCi 3H2O, i.p. (900-1000 h), and were killed 24 h later. Duration of feeding did not influence rates of net fatty acid synthesis or the stimulation by cholesterol of incorporation of newly synthesized fatty acid into hepatic triglyceride and cholesteryl ester.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans
Eriksson, M., L. A. Carlson, et al. (1999), Circulation 100(6): 594-8.
Abstract: BACKGROUND: Apolipoprotein (apo) A-I is the major protein component of HDL, a cholesterol transport particle that protects against atherosclerosis. Apo A-I is believed to promote reverse cholesterol transport, transferring cholesterol from peripheral cells to the liver for subsequent elimination. To test this hypothesis in humans, we measured fecal steroid excretion before and after the intravenous infusion of human proapo A-I (precursor of apo A-I) liposome complexes. METHODS AND RESULTS: Four subjects with heterozygous familial hypercholesterolemia w re studied under standardized conditions. The fecal excretion of bile acids and neutral sterols was determined for 9 days before and 9 days after an intravenous infusion of recombinant human proapo A-I (4 g protein) liposome complexes. Plasma apoA-I and HDL cholesterol levels increased transiently (mean peak concentrations were 64% and 35% above baseline, respectively) during the first 24 hours. Mean lipoprotein lipid and apolipoprotein levels were not different during the 2 collecting periods, however. Serum lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, was also unchanged. The fecal excretion of cholesterol (neutral sterols and bile acids) increased in all subjects (mean increase, +39% and +30%, respectively), corresponding to the removal of approximately 500 mg/d excess cholesterol after infusion. Control infusions with only liposomes in 2 of the patients did not influence lipoprotein pattern or cholesterol excretion. CONCLUSIONS: Infusion of proapoA-I liposomes in humans promotes net cholesterol excretion from the body, implying a stimulation of reverse cholesterol transport. This mechanism may prove useful in the treatment of atherosclerosis.

Stimulation of HMG-CoA reductase as a consequence of phenobarbital-induced primary stimulation of cholesterol 7 alpha-hydroxylase in rat liver
Sudjana-Sugiaman, E., G. Eggertsen, et al. (1994), J Lipid Res 35(2): 319-27.
Abstract: Among nine strains of rat, two were found that responded to phenobarbital treatment with increased activity of hepatic cholesterol 7 alpha-hydroxylase. This effect was maximal after 2-3 days of treatment and was then reduced. Interestingly the increased cholesterol 7 alpha-hydroxylase activity was associated with increased activity of hepatic HMG-CoA reductase in the two responding strains but not in the non-responding strains. In tissues other than the liver, HMG-CoA reductase activity was unaffected in responding rats. Most of the above stimulation occurred at a pretranslatory level and the mRNA levels corresponding to the two enzymes paralleled the activities. The phenobarbital treatment resulted in decreased content of free cholesterol in liver microsomes in a strain of rat that responded with increased cholesterol 7 alpha-hydroxylase activity. It was shown that depletion of cholesterol in the responding strain of rats by lymph fistulation also was associated with a parallel increase in levels of HMG-CoA reductase activity and mRNA. The findings are discussed in relation to the link between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase. A primary upregulation of the cholesterol 7 alpha-hydroxylase by the cytochrome P450 inducer phenobarbital can be expected to lead to increased consumption of cholesterol substrate. This consumption may result in a compensatory increase in the activity of the HMG-CoA reductase. It is suggested that such a mechanism is responsible for part of the covariation of the two enzyme systems under different conditions.

Stimulation of microsomal cholesterol ester hydrolase by glucagon, cyclic AMP analogues, and vasopressin in isolated rat hepatocytes
Hernandez, M. L., M. J. Martinez, et al. (1996), Lipids 31(3): 269-76.
Abstract: Short-term activation of microsomal cholesterol ester hydrolase by glucagon, cAMP analogues, and vasopressin in isolated rat hepatocytes is described. Glucagon led to a dose- and time-dependent activation of cholesteryl oleate hydrolysis, but values returned to basal levels within 120 min. Exposure of isolated hepatocytes to 0.5 mM concentrations of dibutyryl-cAMP or 8-4-chlorophenylthio-cAMP, or 25 microM forskolin caused persistent activation of cholesterol ester hydrolase activity after a lag period of 30 min. The three agents resulted in early marked intracellular accumulation of cAMP that declined progressively, and moderate and sustained reductions in the diacylglycerol content. The actions of glucagon on hepatocytes were inhibited by pretreatment of cells with 10 nM 8-arginine vasopressin. Vasopressin elicited a consistent and sustained increase in cholesterol ester hydrolase activity and diacylglycerol without affecting cAMP while reducing the effect of glucagon on cAMP. Furthermore, the effects of glucagon and vasopressin on the activation of cholesterol ester hydrolase were not additive despite the similarity of their stimulation of diacylglycerol formation. Blockade of vasopressin-mediated activation of cholesterol ester hydrolase and diacylglycerol content were induced by excess prazosin. These data suggest that stimulation of microsomal cholesterol ester hydrolase in isolated liver cells may involve at least two signal transduction systems.

Stimulation of progesterone production in human granulosa-lutein cells by lipoproteins: evidence for cholesterol-independent actions of high-density lipoproteins
Ragoobir, J., D. R. Abayasekara, et al. (2002), J Endocrinol 173(1): 103-11.
Abstract: Low-density lipoproteins (LDL) have been consistently reported to stimulate ovarian steroidogenesis, apparently by the provision of cholesterol as a steroidogenic substrate. Recent studies suggest that high-density lipoproteins (HDL) can also deliver cholesterol to support progesterone synthesis in human granulosa-lutein cells. Therefore, this study investigated the contributions of (i) cholesterol delivery, (ii) cyclic AMP and (iii) protein kinase C (PKC) in the steroidogenic responses of human granulosa-lutein cells to HDL and LDL. Over a 24-h treatment incubation, HDL stimulated a larger increase in progesterone output than did LDL at equivalent cholesterol concentrations. Moreover, at equal protein concentrations (100 microg protein/ml), HDL doubled progesterone production by cells co-treated with a maximally effective concentration of 22R-hydroxycholesterol, whereas LDL had no effect on the progesterone response to this membrane-permeable sterol. These observations indicate that the progesterone response to HDL is not solely due to the delivery of cholesterol as a steroidogenic substrate. Over 24 h, the stimulation of progesterone synthesis by HDL was additive with the response to a maximally effective concentration of dibutyryl-cAMP, but was unaffected by the down-regulation of PKC activity (by chronic pre-treatment with a tumour-promoting phorbol ester). We have concluded that HDL appears to stimulate progesterone production in human granulosa-lutein cells by a mechanism not solely reliant on cholesterol delivery.

Stoichiometry of cholesterol-sphingomyelin condensed complexes in monolayers
Radhakrishnan, A., X. M. Li, et al. (2001), Biochim Biophys Acta 1511(1): 1-6.
Abstract: Some binary mixtures of cholesterol and phospholipids in monolayers have thermodynamic phase diagrams with two upper miscibility critical points. This feature has been interpreted in terms of 'condensed complexes' between the phospholipid and cholesterol. The present work gives evidence for the formation of complexes with a common simple integral stoichiometry in binary mixtures of cholesterol and a series of five sphingomyelins where the amide-linked acyl chain length is varied. This indicates that these complexes have a distinct geometry even though they form a liquid phase.

Stop the cholesterol campaign!
Ravnskov, U. (1993), Lakartidningen 90(50): 4587-8; discussion 4589-90.

Strain-dependent differences in the pattern of aortic lipid deposition in cholesterol-fed rabbits
Barnes, S. E. and P. D. Weinberg (2001), Exp Mol Pathol 71(2): 161-70.
Abstract: Spontaneous lesions develop downstream of branch points in immature human and rabbit aortas, but occur more frequently at the sides and upstream of these sites in mature vessels. Cholesterol-induced lesions in mature rabbits, however, have shown the downstream distribution in one trial and the more upstream distribution in another. We tested the hypothesis that this discrepancy reflected a difference in the degree of impairment of the nitric oxide pathway. Mature rabbits were fed cholesterol-enhanced versions of the two base diets used in the previous trials, and some were given additional vitamin E or l-arginine to protect the NO pathway or L-NAME to inhibit it. Unexpectedly, the rabbits developed a lesion pattern intermediate between the two previously described, and this distribution was unaffected by the base diet or supplements. Consequently, an exploratory study was conducted to investigate possible effects of other differences between the two earlier trials. These were the precise age of the mature rabbits and the feeding protocol employed; both base diets again were used. Two different lesion patterns were observed in this trial, but there was no systematic effect of any of the controlled variables. Instead, there appeared to be an influence of the supplier from which the rabbits had been obtained. A multivariate analysis of all four trials confirmed that the pattern of disease was associated with rabbit strain, and not with base diet, cholesterol level, or precise age.

Strategies for increasing house staff management of cholesterol with inpatients
Boekeloo, B. O., D. M. Becker, et al. (1990), Am J Prev Med 6(2 Suppl): 51-9.
Abstract: This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.

Strategies for the improvement of an amperometric cholesterol biosensor based on electropolymerization in flow systems: use of charge-transfer mediators and platinization of the electrode
Vidal, J. C., E. Garcia-Ruiz, et al. (2000), J Pharm Biomed Anal 24(1): 51-63.
Abstract: Different configurations based on an amperometric biosensor with cholesterol oxidase entrapped in a polypyrrole film have been developed with a view to improving the analytical properties of this biosensor. The alternatives considered involve the simultaneous entrapment of the enzyme and a charge-transfer mediator as well as previous platinization of the surface of the Pt electrode. Both artificial (a ferrocene derivative) and natural (flavin nucleotides) mediators were studied as constituents of the charge-transfer process between the enzyme and the electrode. The comparative study of these biosensors, which were prepared in situ in a continuous flow system, made it possible to determine the advantages and disadvantages of each configuration when applied to flow-injection determination of cholesterol.

Strategies for using university health services for cholesterol screening
Hoffman, C. J. and T. Turner (1994), J Am Coll Health 43(2): 86-9.
Abstract: Seven hundred seventy students, parents, and employees participated in free cholesterol screenings during key promotional events at Central Michigan University between 1989 and 1992. Participants were self-selected volunteers who wanted to know their cholesterol levels. More than one third of the participants (32.4% of the students, 38.0% of the parents, and 54.3% of the employees) were found to have borderline or high cholesterol readings that put them at risk of coronary artery disease (CAD) because of hypercholesterolemia. The screening may have attracted subjects with a family history of CAD or other risk factors, and these individuals need follow-up lipid profiles and cholesterol education. The authors provide a description of the innovative approaches of their program and offer suggestions for promotional cholesterol screening programs.

Strength training does not alter the effects of testosterone propionate injections on high-density lipoprotein cholesterol concentrations
Frisch, F. and K. D. Sumida (1999), Metabolism 48(12): 1493-7.
Abstract: The purpose of the study was to examine the long-term effects of a high-volume strength training program (vertical ladder climbing) and testosterone propionate injections (intraperitoneal) on serum lipid and lipoprotein concentrations in male Sprague-Dawley rats. The animals were randomly divided into a testosterone (T)-treated group (dose per injection, 2.5 mg/kg testosterone propionate solubilized in 1 mL safflower oil) and a control (C) group (injected with an isovolumic amount of safflower oil alone). Animals were further divided into a strength-trained group (E) and a sedentary group (S). The 10-week resistance training program consisted of weights (100% of body mass) appended to the tail as the animal climbed an 85-cm ladder to volitional fatigue. Following 10 weeks of strength training and testosterone injections, body weight was not significantly different between the main effects of strength training exercise (TE + CE v TS + CS) and testosterone injections (TE + TS v CE + CS) or between groups. Testicular mass (mean +/- SE) was measured as a relative indicator of testosterone effects. Both TE and TS had significantly reduced testicular mass (2.56 +/- 0.04 and 2.38 +/- 0.03 g, respectively) compared with CE and CS (3.49 +/- 0.03 and 3.49 +/- 0.04 g, respectively). No significant differences were observed between groups for total serum cholesterol, serum triglycerides, or serum low-density lipoprotein cholesterol (LDL-C). In contrast, significant decreases in high-density lipoprotein cholesterol (HDL-C) were observed for both TE (26.7 +/- 1.6 mg/dL) and TS (27.5 +/- 1.3 mg/dL) compared with CE (48.7 +/- 2.9 mg/dL) and CS (43.5 +/- 2.6 mg/dL). As a result, the total cholesterol to HDL-C ratio was significantly greater for TS + TE (4.7 +/- 0.1) compared with CS + CE (2.9 +/- 0.2). These observations suggest that in animals, a 10-week program of high-volume strength training does not elicit any beneficial effect on the lipid or lipoprotein status, nor does it attenuate the altered lipoprotein profile induced by testosterone propionate injections.

Streptomyces: a superior source for cholesterol oxidase used in serum cholesterol assay
Lolekha, P. H. and Y. Jantaveesirirat (1992), J Clin Lab Anal 6(6): 405-9.
Abstract: The present study compared three cholesterol oxidase sources (Nocardia, Streptomyces, and Pseudomonas sps.) for serum cholesterol assay. We found cholesterol oxidase isolated from Streptomyces was superior than those isolated from Nocardia and Pseudomonas sps. Performances of the reagent contained Streptomyces cholesterol oxidase was excellent and comparable to the performances obtained from reagent contained Nocardia cholesterol oxidase. Moreover, the reagent containing Streptomyces cholesterol oxidase had the lowest cost and had the longest shelf-life ($U.S. 0.17/mL, 10 weeks) compared to the reagent contained Nocardia ($U.S. 0.50/mL, 8 weeks) or Pseudomonas ($U.S. 0.20/mL, 6 weeks) cholesterol oxidase.

Streptozotocin-induced diabetic cynomolgus monkey is a model of hypertriglyceridemia with low high-density lipoprotein cholesterol
Tsutsumi, K., T. Iwamoto, et al. (1998), Biol Pharm Bull 21(7): 693-7.
Abstract: Hypertriglyceridemia with low high-density lipoprotein (HDL) cholesterol is a risk factor of cardiovascular disease. We attempted to create an animal model of hypertriglyceridemia with low HDL cholesterol by intravenously injecting 30 mg/kg body weight streptozotocin (STZ) to cynomolgus monkeys. This induced hypoinsulinemia and resulted in a decrease in postheparin plasma lipoprotein lipase (LPL) activity and LPL enzyme mass, reduction of plasma HDL cholesterol and elevation of triglycerides. Low HDL cholesterol subsequently caused a reduction of HDL2b cholesterol, while hypertriglyceridemia caused an elevation of very low-density lipoprotein (VLDL) triglyceridemia. Apolipoprotein CII, a co-factor of LPL, was not affected by STZ administration. These results show that hypertriglyceridemia with low HDL cholesterol results from a reduction of LPL activity without affecting apolipoprotein CII after STZ administration. The STZ-induced diabetic cynomolgus monkey is a model of hypertriglyceridemia with low HDL cholesterol, and may be potentially beneficial for studying atherosclerosis caused by hypertriglyceridemia with low HDL cholesterol.

Streptozotocin-induced increase in cholesterol ester transfer protein (CETP) and its reversal by insulin in transgenic mice expressing human CETP
Cheema, S. K. and F. Rashid-Kolvear (2003), Can J Physiol Pharmacol 81(10): 997-1004.
Abstract: High plasma triacylglycerol and low high-density lipoprotein levels are risk factors for cardiovascular disease in diabetes. Plasma high-density lipoprotein levels are regulated by cholesterol ester transfer protein (CETP). The regulation of CETP under diabetic conditions is not clear, and this is due to a lack of appropriate models. We used transgenic mice expressing human CETP to study the regulation of this protein under type-1 diabetic conditions and further investigated whether insulin reverses the effect of diabetes. Mice expressing human CETP under the control of its natural flanking region and age-matched littermates not expressing this protein were made diabetic by injecting streptozotocin, and the reversal of diabetes was assessed by injecting insulin. The plasma total cholesterol, low-density lipoprotein-cholesterol, and triacylglycerol concentrations were elevated, whereas high-density lipoprotein-cholesterol concentrations were reduced after the onset of diabetes. Insulin injection partially recovered this effect. The plasma cholesterol ester transfer activity, CETP mass, and hepatic CETP mRNA abundance were significantly higher in diabetic mice that were partially restored by insulin administration. There was a strong correlation between high-density lipoprotein-cholesterol concentrations and cholesterol ester transfer activity. These results suggest that an increase in CETP under diabetic conditions might be a major factor responsible for increased incidence of diabetes-induced atherosclerosis.

Stress modulates cholesterol-induced changes in plasma and liver fatty acid composition in rats fed n-6 fatty acid-rich oils
Huang, Y. S., D. E. Mills, et al. (1990), Proc Soc Exp Biol Med 195(1): 136-41.
Abstract: The effects of dietary cholesterol (CH) and isolation stress on fatty acid compositions of plasma and liver cholesteryl ester and phospholipids were compared in growing rats fed an 18:2n-6 or an 18:3n-6 enriched semisynthetic diet for 2 weeks. Stress, CH-feeding, and dietary fats had no significant effects on plasma CH level, but CH-feeding alone elevated the liver CH concentrations. CH-feeding also modulated the liver polyunsaturated fatty acid compositions, i.e., increasing 18:2n-6 levels, and reducing 20:4n-6 levels, indicating an inhibition of the enzymes, delta-6 and delta-5-desaturases. The extent of these changes was less in rats fed 18:3n-6 than in those fed 18:2n-6. Stress, which alone had no significant effects on plasma and liver fatty acid compositions, attenuated the CH-induced changes of fatty acid levels.

Stricter cholesterol guidelines broaden indications for the 'statin' drugs
Capriotti, T. (2003), Medsurg Nurs 12(1): 51-7.

Stroke and cholesterol: weakness of risk versus strength of therapy
Donnan, G. A. and S. M. Davis (2004), Stroke 35(6): 1526.

Stroke prevention, blood cholesterol, and statins
Amarenco, P., P. Lavallee, et al. (2004), Lancet Neurol 3(5): 271-8.
Abstract: The risk of stroke increases with age, and hence the disease particularly affects the elderly, who are also at high risk for coronary heart disease. Epidemiological and observational studies have not shown a clear association between cholesterol concentrations and all causes of stroke. Large, long-term statin trials in patients with established or high risk for coronary heart disease have shown that statins decrease stroke incidence. These statin trials in a combined total of 70,020 patients indicate relative and absolute risk reductions for stroke of 21% and 0.9%, respectively. By comparison, the number of strokes prevented per 1000 patients treated for 5 years in patients with coronary heart disease is nine for statins versus 17.3 for antiplatelet drugs and 17 for antihypertensive drugs. Although the Heart Protection Study showed that statins lower the risk of major coronary events in patients with a previous stroke, statins may not lower stroke recurrence in these patients. In this review, we discuss the potential reasons for the effects of statins on stroke and the mechanisms of action. Treatment strategies on the basis of global cardiovascular risk may be most effective. Additional studies in patients representative of the typical stroke population are needed.

Cholesterol Articles and Abstracts

Cholesterol Journal Articles