| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Beyond cholesterol: the enigma of atherosclerosis revisited Bhakdi, S., K. J. Lackner, et al. (2004), Thromb Haemost 91(4): 639-45. Abstract: Atherosclerosis is widely regarded as a chronic inflammatory disease that develops as a consequence of entrapment of low density lipoprotein (LDL) in the arterial intima. Native LDL lacks inflammatory properties, so the lipoprotein must undergo biochemical alterations in order to become atherogenic. Modification is commonly regarded as being dangerous because it bestows inflammatory properties onto the lipoprotein. Most current models consider oxidation to be the decisive modifying event. Here, we submit a different concept for discussion. We propose that modification of tissue-entrapped LDL is required because it enables the lipoprotein to signal to the immune system and effect its own removal. Oxidation would be too haphazard to fulfill this function. We summarize the evidence indicating that modification occurs through the action of ubiquitous hydrolytic enzymes. Enzymatically remodeled LDL binds C-reactive protein. C-reactive protein bound to remodeled LDL not only activates complement but also regulates it by inhibiting activation of the terminal complement cascade. Simultaneously, epitopes are exposed to enable the lipoprotein to be recognized and taken up by macrophages. The high density lipoprotein-dependent reverse transport pathway concludes the sequence of events that clear tissues of cholesterol in a non-inflammatory manner very similar to what has been described for the removal of apoptotic cells. It is proposed that these physiological processes occur throughout life without harm, pathology evolving only when the machinery suffers overload. Detrimental effects are then evoked primarily by the unreigned activation of complement, macrophages, and other effectors of the immune system in the lesions. |
| Beyond cholesterol--inflammatory cytokines, the key mediators in atherosclerosis Mangge, H., H. Hubmann, et al. (2004), Clin Chem Lab Med 42(5): 467-74. Abstract: The development of atherosclerotic lesions encompasses a cascade of cellular and molecular responses that can at best be characterized as an inflammatory process, and exhibits striking similarities to autoimmune diseases, such as rheumatoid arthritis. Chemokines, cytokines and their receptors are critically involved in initiation and perpetuation of atherosclerosis, and they play important roles at all levels in the pathogenesis of this disease. In the present article, the currently available information on cytokines and chemokines as key mediators in atherosclerosis is reviewed. Furthermore, based on recent experiences of our own with very early stages of atherosclerosis, possible new ways to make use of these parameters toward improved early detection, prevention and treatment of this disease are indicated. |
| Beyond LDL cholesterol reduction Superko, H. R. (1996), Circulation 94(10): 2351-4. |
| Beyond LDL-cholesterol: can further reductions in CAD risk be achieved by considering triglycerides? Davignon, J. and T. A. Pearson (1998), Can J Cardiol 14 Suppl B: 2B. |
| Beyond low-density lipoprotein cholesterol. A perspective on low high-density lipoprotein disorders and Lp(a) lipoprotein excess Rosenson, R. S. (1996), Arch Intern Med 156(12): 1278-84. Abstract: Evidence supports the involvement of 2 common dyslipidemias---low high-density lipoprotein disorders and Lp(a) lipoprotein excess--in coronary heart disease. Until clinical trials determine whether specific therapeutic interventions can prevent the occurrence and recurrence of coronary heart disease in patients with these dyslipidemias, the implementation of cholesterol-lowering guidelines can provide a reasonable way to manage low high-density lipoprotein disorders and to identify specific categories of patients who may be at particularly high risk for premature coronary heart disease. Empiric treatment guidelines are suggested for low high-density lipoprotein disorders and Lp(a) lipoprotein excess in order to foster further discussion and validation by clinical trial data. |
| Beyond the cholesterol profile: monitoring therapeutic effectiveness of statin therapy Schwartz, R. G. (2001), J Nucl Cardiol 8(4): 528-32. |
| Bezafibrate therapy in patients with isolated low high-density lipoprotein cholesterol levels may have a beneficial effect in prevention of atherosclerosis Weintraub, M. S., I. Grosskopf, et al. (1995), Metabolism 44(11): 1401-9. Abstract: Although a low plasma high-density lipoprotein cholesterol (HDL-C) level is a well-accepted risk factor for coronary artery disease (CAD), it is unclear whether pharmacologic agents can effectively increase HDL-C levels and/or reduce the incidence of CAD in patients with isolated low HDL-C levels. An important determinant of HDL levels is the efficiency of postprandial lipoprotein catabolism. The purpose of the present study was to evaluate the efficacy of bezafibrate therapy in increasing HDL-C levels in these patients and to examine its effect on postprandial lipoprotein levels. Fasting and postprandial lipid and lipoprotein levels were studied in 23 patients with isolated low HDL-C levels before and during 3 and 6 months of bezafibrate treatment. Postprandial lipoprotein levels were evaluated using the vitamin A-fat loading test, in which these intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Patients with isolated low HDL had significantly higher levels of chylomicron RP than a control group of 19 normolipidemic subjects. The area below the chylomicron RP curve was 17,773 +/- 6,821 versus 13,936 +/- 6,217 micrograms/L.h, respectively (P <.005). No differences were found in chylomicron remnant levels between the groups. Bezafibrate therapy reduced the chylomicron RP area by 27%, from 17,773 +/- 6,821 to 12,895 +/- 2,576, and the nonchylomicron RP area by 25%, from 6,059 +/- 3,310 to 4,430 +/- 1,963 (P <.0001). It increased fasting HDL-C levels from 35 +/- 3 to 38 +/- 1.4 mg/dL after 3 months (P <.001) and to 40 +/- 2.2 mg/dL after 6 months (P <.001).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Bicarbonate stimulated phospholipid scrambling induces cholesterol redistribution and enables cholesterol depletion in the sperm plasma membrane Flesch, F. M., J. F. Brouwers, et al. (2001), J Cell Sci 114(Pt 19): 3543-55. Abstract: Mammalian sperm cells are activated prior to fertilization by high bicarbonate levels, which facilitate lipoprotein-mediated cholesterol efflux. The role of bicarbonate and cholesterol acceptors on the cholesterol organization in the sperm plasma membrane was tested. Bicarbonate induced an albumin-independent change in lipid architecture that was detectable by an increase in merocyanine staining (due to protein kinase A-mediated phospholipid scrambling). The response was limited to a subpopulation of viable sperm cells that were sorted from the non-responding subpopulation by flow cytometry. The responding cells had reduced cholesterol levels (30% reduction) compared with non-responding cells. The subpopulation differences were caused by variable efficiencies in epididymal maturation as judged by cell morphology. Membrane cholesterol organization was observed with filipin, which labeled the entire sperm surface of non-stimulated and non-responding cells, but labeled only the apical surface area of bicarbonate-responding cells. Addition of albumin caused cholesterol efflux, but only in bicarbonate-responding cells that exhibited virtually no filipin labeling in the sperm head area. Albumin had no effect on other lipid components, and no affinity for cholesterol in the absence of bicarbonate. Therefore, bicarbonate induces first a lateral redistribution in the low cholesterol containing spermatozoa, which in turn facilitates cholesterol extraction by albumin. A model is proposed in which phospholipid scrambling induces the formation of an apical membrane raft in the sperm head surface that enables albumin mediated efflux of cholesterol. |
| Bidirectional transport of cholesterol between gallbladder epithelial cells and model bile Hayashi, A. and S. P. Lee (1996), Am J Physiol 271(3 Pt 1): G410-4. Abstract: Lipids in hepatic bile may be modified by the gallbladder epithelium. The purpose of this study was to demonstrate a bidirectional exchange of cholesterol between biliary lipid carriers and gallbladder epithelial cells and to determine the factors regulating this cholesterol transfer. Gallbladder epithelial cells were cultured to confluent monolayers, their membranes were labeled with endogenously synthesized 14Ccholesterol, and the cells were incubated with model bile introduced into the apical membrane compartment. Similarly, model bile with different lipid composition containing 3Hcholesterol was incubated with the unlabeled monolayers. We found that cholesterol in the apical membrane bilayer of the epithelial cells exchanged readily with that in bile, but only in the presence of bile salts. The rate of exchange is dependent on the concentration and species of bile salts. The net gain of cholesterol (absorption) or net loss of cholesterol (cytotoxicity) exhibited by the epithelial cells was regulated by the thermodynamic stability of cholesterol and the detergent effect of mixed micelles in bile. It is also possible that the physicochemical composition of lipids in bile may modify the cellular function of the gallbladder epithelium. |
| Bifidobacteria strain behavior toward cholesterol: coprecipitation with bile salts and assimilation Tahri, K., J. P. Grill, et al. (1996), Curr Microbiol 33(3): 187-93. Abstract: Resting cells and growing cells of bifidobacteria strains exhibited an ability to remove cholesterol in the presence of bile salts. In resting cell assays, the removed cholesterol was precipitated in the presence of cholic acid at pH values lower than 5.4. However, this precipitated cholesterol was redissolved when the pellets were washed with phosphate buffer, pH 7, and no cholesterol was found in the cells. It appears that this precipitation is a transient phenomenon. In the case of growing cells, the removed cholesterol was partially recovered when cells were washed with phosphate buffer, pH 7, while the remaining cholesterol was extracted from the cells. Cultured in the presence of radiolabeled free or esterified cholesterol, bifidobacteria strains were able to assimilate esterified cholesterol. It is concluded that the removal of cholesterol from the growth medium by bifidobacteria strains is due to both bacterial assimilation and precipitation of cholesterol. |
| Bilateral cholesterol granuloma: an unusual presentation as an intradural mass Henick, D. H. and J. G. Feghali (1994), J Otolaryngol 23(1): 15-8. Abstract: The origin of the cholesterol granuloma is controversial; however, it is believed to result from an inflammatory response of the temporal bone to an obstruction of the pneumatized air cells. Hemorrhage into the air cells results in a foreign-body reaction and progressive granuloma formation. As the process develops, bone is eroded by this expansile lesion, often involving the middle ear, the petrous apex, and the cerebellopontine angle. We present the first reported case of cholesterol granulomas manifesting as bilateral intradural lesions adjacent to the temporal lobes. The fact that it presents bilaterally with sclerotic mastoids makes this presentation even more unique. Its location might cast controversy on the existing theories of development. A literature review of the cholesterol granuloma will be discussed, relating it to this patient's unusual presentation. |
| Bilateral cholesterol granulomas of the temporal bone Eby, T. L. and B. L. Guthrie (1998), ORL J Otorhinolaryngol Relat Spec 60(6): 318-21. Abstract: Cholesterol granulomas of the temporal bone without clinical symptoms of chronic otitis media may result from an indolent inflammatory process caused by a congenitally blocked group of air cells. A unique case of giant bilateral cholesterol granulomas of the temporal bone is presented to support this theory. Management allowed bilateral surgical removal with hearing preservation. The differentiation between cholesterol granuloma, giant cholesterol cyst and other lesions of the temporal bone is discussed. The presumed pathogenesis of this condition is reviewed. |
| Bilayer thickness in unilamellar extruded 1,2-dimyristoleoyl and 1,2-dierucoyl phosphatidylcholine vesicles: SANS contrast variation study of cholesterol effect Gallova, J., D. Uhrikova, et al. (2004), Colloids Surf B Biointerfaces 38(1-2): 11-4. Abstract: Small-angle neutron scattering on extruded unilamellar vesicles in water was used to study bilayer thickness when cholesterol (CHOL) was added at 44.4 mol% to 1,2-dimyristoleoylphosphatidylcholine (diC14:1PC) and 1,2-dierucoylphosphatidylcholine (diC22:1PC) bilayers. Using the (1)H(2)O/(2)H(2)O contrast variation and the small-angle form of Kratky-Porod approximation, the bilayer gyration radii at infinite contrast R(g,infinity) and the bilayer thickness parameters d(g,infinity) = 12(0.5)R(g,infinity) were obtained at 30 degrees C. Addition of cholesterol to diC14:1PC increased the d(g,infinity) from 3.72 +/- 0.02 to 4.26 +/- 0.01 nm, while in the diC22:1PC bilayers the d(g,infinity) change observed was within the experimental error: +0.23 +/- 0.23 nm. |
| Bile acid and phospholipid fatty acid composition in bile of patients with cholesterol and pigment gallstones van Erpecum, K. J., G. P. van Berge Henegouwen, et al. (1991), Clin Chim Acta 199(3): 295-303. Abstract: It has been previously reported that patients with cholesterol gallstones have increased biliary deoxycholate and arachidonate content as compared with normal subjects without gallstones. Increased biliary deoxycholate and arachidonate content might be a primary factor in the pathogenesis of cholesterol gallstones or merely an epiphenomenon due to the presence of gallstones. We therefore compared biliary bile acid composition in 46 patients with cholesterol gallstones and 22 patients with pigment stones. In addition, biliary phospholipid fatty acid composition was determined in 44 of these patients (30 cholesterol and 14 pigment stone patients). No significant differences were detected. In particular, the percentage deoxycholic acid (mean +/- SD: 20.3 +/- 8.8% and 21.5 +/- 10.9% respectively) and the percentage arachidonic acid (4.4 +/- 2.0% and 4.5 +/- 2.2%, respectively) were very similar. A significant correlation between age and biliary cholesterol saturation index was found only for the group of patients with pigment stones (R = 0.52, p less than 0.02). In conclusion, the present study does not support a primary role for increased biliary deoxycholic acid or arachidonic acid in the pathogenesis of cholesterol gallstones. |
| Bile acid and very low density lipoprotein production by cultured hepatocytes from hypo- or hyperresponsive rabbits fed cholesterol Podrez, E. A., V. A. Kosykh, et al. (1993), Lipids 28(8): 709-13. Abstract: Two groups of rabbits, either hyperresponsive or hyporesponsive to dietary cholesterol, were selected after ten weeks of cholesterol feeding (0.2 g cholesterol/kg body weight per day). Bile acids and very low density lipoprotein (VLDL) production were determined in primary hepatocyte cultures from control, hyper- and hyporesponsive rabbits. Free cholesterol and cholesteryl ester contents in hepatocytes of the hyperresponsive rabbits was significantly increased. In contrast, lipid composition in hepatocytes of the hyporesponders was similar to that of control cells. Cholic acid was the predominant bile acid in the culture medium of hepatocytes together with small amounts of chenodeoxycholic and deoxycholic acids. The rate of cholic acid production by hepatocytes in the hyporesponsive group was two times higher than that in the hyperresponsive group. Bile acid production by control hepatocytes was slightly higher than in the hyperresponsive group. In contrast, secretion of VLDL cholesteryl ester was significantly increased by hepatocytes of the hyperresponsive rabbits. Similar differences in bile acid production were found between hypo- and hyperresponsive rabbits selected after five days of cholesterol feeding and subsequent maintenance on a low cholesterol diet for a period of one month. The results suggest that the increased rate of bile acid production could contribute to the apparent resistance of hyporesponders to the atherogenic diet. |
| Bile acid excretion and cholesterol 7 alpha-hydroxylase expression in hypercholesterolemia-resistant rabbits Poorman, J. A., R. A. Buck, et al. (1993), J Lipid Res 34(10): 1675-85. Abstract: We have developed a partially inbred substrain of New Zealand white rabbits (CRT/mlo) that are resistant to the hypercholesterolemia that accompanies cholesterol feeding to normal rabbits. The plasma cholesterol concentration of normal rabbits increases dramatically from about 30 mg/dl to > 300 mg/dl after they are fed a 0.1% cholesterol-enriched diet for 3-4 months. Cholesterol-fed CRT/mlo animals, however, maintain a cholesterol level of about 30 mg/dl during the entire cholesterol feeding period. In addition to the low plasma cholesterol level, measurements of cellular cholesterol indicate that the hepatic cholesterol content of the cholesterol-fed resistant rabbit remains markedly lower than it does in normal animals fed the same diet. The only mechanism for removal of significant quantities of cholesterol carbon from the body is via the fecal excretion of cholesterol, neutral sterol metabolites, and bile acids. In comparison to the basal, low-cholesterol diet, we observed that cholesterol-fed resistant rabbits had increased excretion of lithocholic acid, while excretion of this bile acid by cholesterol-fed normal rabbit remained similar to basal diet levels. Deoxycholic acid excretion, the other main bile acid excreted in the feces of rabbits, was decreased in response to cholesterol challenge in animals with either resistant or normal phenotypes, but the decrease was significantly less in the resistant rabbits. Thus, the resistant rabbits excreted relatively more lithocholic and deoxycholic acid than did the cholesterol-fed normal rabbit. The difference in bile acid excretion was also manifest by a higher than normal level of cholesterol 7 alpha-hydroxylase activity and cholesterol 7 alpha-hydroxylase mRNA in the livers from resistant versus normal rabbits. As cholesterol 7 alpha-hydroxylase is the putative rate-limiting step of bile acid synthesis, we believe that the increased excretion of bile acids by resistant animals is due, at least in part, to increased levels of cholesterol 7 alpha-hydroxylase expression. |
| Bile acid metabolism and its role in human cholesterol balance Everson, G. T. (1992), Semin Liver Dis 12(4): 420-8. |
| Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism Einarsson, K., S. Ericsson, et al. (1991), Eur J Clin Pharmacol 40 Suppl 1: S53-8. Abstract: Interruption of the enterohepatic circulation of bile acids by cholestyramine or colestipol influences the hepatic metabolism of cholesterol in many ways. The synthesis of bile acids is increased, as reflected by a several-fold increase in the activity of the cholesterol 7 alpha hydroxylase, the rate-determining enzyme in bile acid synthesis. The increased metabolism of cholesterol to bile acids causes an enhanced demand of cholesterol in the hepatocytes which respond with both new synthesis of cholesterol, as reflected in a several-fold increase of the HMG-CoA reductase activity, and increased expression of LDL receptors. As a consequence, the plasma level of LDL-cholesterol is lowered. The hepatic secretion rate of VLDL particles is increased. Cholestyramine therapy does not affect the output of biliary lipids or the cholesterol saturation of bile, indicating that treatment with bile acid sequestrants should not be associated with any increased risk of gallstone formation. |
| Bile acid sulfonates alter cholesterol gallstone incidence in hamsters Cohen, B. I., S. Miki, et al. (1993), Hepatology 17(1): 103-10. Abstract: The prevention of cholesterol gallstone formation by three bile acid analogs, sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24- sulfonate, sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane-24-sulfonate, was examined in a hamster model of cholesterol cholelithiasis. Sodium taurochenodeoxycholate, sodium tauroursodeoxycholate and sodium taurohyodeoxycholate were studied simultaneously for comparison. Gallstones and cholesterol crystals were induced in 14 of 15 hamsters fed a bile acid-free, semipurified lithogenic diet containing 0.3% cholesterol and 4% butterfat for 6 wk. The addition of 0.1% sodium taurochenodeoxycholate and sodium tauroursodeoxycholate to the lithogenic diet had little effect on the formation of gallstones or biliary cholesterol crystals. In contrast, sodium 3 alpha,7 alpha-hydroxy-5 beta-cholane-24- sulfonate and sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate, when fed at the same dose, prevented cholesterol gallstone formation significantly. Sodium taurohyodeoxycholate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane- 24-sulfonate inhibited cholesterol gallstone formation effectively. The cholesterol saturation index of bile was greater than 1.00 in all groups, with the exception of the group fed sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate. Liver and serum cholesterol levels tended to be lower in most of the groups that were fed bile acids. This effect was most pronounced in the animals receiving sodium taurohyodeoxycholate. At the end of the experiment, the administered sulfonate analogs were detected in gallbladder bile.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Bile acid synthesis from cholesterol: regulatory and auxiliary pathways Javitt, N. B. (1994), Faseb J 8(15): 1308-11. Abstract: Bile acid synthesis from cholesterol can occur via two pathways, one initiated by sterol 27-hydroxylase activity or one initiated by that of cholesterol 7 alpha-hydroxylase. In contrast to cholesterol 7 alpha-hydroxylase, which is found in the liver, sterol 27-hydroxylase is a widely distributed mitochondrial enzyme with high activity in vascular endothelial cells. Although both pathways lead to the production of chenodeoxycholic and cholic acids, the key step, 7 alpha-hydroxylation, is governed by two different enzymes. Both 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid, the metabolites of cholesterol occurring via sterol 27-hydroxylase activity, normally circulate in plasma. After their uptake by the liver they are metabolized mostly to chenodeoxycholic acid, which down-regulates the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting step for the production of bile acids in the liver. Because of this relationship and also in view of the accelerated atherosclerosis and cholesterol deposition in tissues that occur as a consequence of genetically determined sterol 27-hydroxylase deficiency and of the potent biologic effect of 27-hydroxycholesterol in cell culture, it is proposed that this metabolic pathway serves a regulatory function. The pathway beginning with cholesterol 7 alpha-hydroxylation is modulated by genetic, hormonal, and probably dietary factors, and becomes most prominent with the interruption of the enterohepatic circulation of bile acids. |