| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol as a predictor of progression in nondiabetic chronic renal disease Greco, B. A. and J. A. Breyer (1997), Contrib Nephrol 120: 48-61. Abstract: In summary, then, there is an accumulating body of clinical human data supporting the concept that lipid nephrotoxicity may be important in the initiation of renal injury, and that lipids play a synergistic role in the inexorable process of progression to end-stage renal disease in nondiabetic as well as diabetic chronic renal disease. Further clarification of the role of lipid nephrotoxicity and impact of therapeutic interventions await data from larger prospective studies aimed at this specific question. |
| Cholesterol as a risk factor for coronary heart disease Tunstall-Pedoe, H. and W. C. Smith (1990), Br Med Bull 46(4): 1075-87. Abstract: The intense current interest in lipids as causal risk factors in coronary heart disease has encouraged a unifactorial, one-dimensional approach to coronary risk based on fixed total serum cholesterol or low density lipoprotein (LDL) cholesterol cut-points. Epidemiological evidence shows that coronary heart disease risk is multifactorial; the risk associated with a given lipid value is modulated overwhelmingly by the level or presence of other factors. While populations with high lipid values may be characterized as being at high risk, individual risk cannot be determined by isolated lipid measurements. To characterize individuals as at high or low risk by considering lipid values alone results in serious misclassification. Cut-points derived from middle-aged American men create anomalies when applied to different age and sex groups and to different populations. Clinical management of risk factors in individuals should involve the negotiation of a flexible and multi-dimensional individual regime, comprising all modifiable factors. |
| Cholesterol as a risk factor for coronary heart disease in elderly men. The Baltimore Longitudinal Study of Aging Sorkin, J. D., R. Andres, et al. (1992), Ann Epidemiol 2(1-2): 59-67. Abstract: In order to explore the relationship of cholesterol to coronary heart disease (CHD), defined as angina pectoris, myocardial infarction, and sudden coronary death, in older men, a group of 1052 men, participants in the Baltimore Longitudinal Study on Aging, were examined. Subjects were stratified into three age groups, 28 to 64, 65 to 74, and 75 to 97 years old. In all three age groups, cholesterol was a significant risk factor for CHD. In the oldest age group (n = 250), the relationship between cholesterol and risk was linear (P =.003) as opposed to younger age groups where the relationship was exponential. This study extends the age range in which hypercholesterolemia has been shown to be associated with CHD to include the 75- to 97-year range. |
| Cholesterol as a risk factor for stroke: the fugitive? Piechowski-Jozwiak, B. and J. Bogousslavsky (2004), Stroke 35(6): 1523-4. |
| Cholesterol as a singlet oxygen detector in biological systems Girotti, A. W. and W. Korytowski (2000), Methods Enzymol 319: 85-100. Abstract: In cells under oxidative attack, membrane Ch, through the formation of its signature hydroperoxide and diol products, can serve as a unique detector in situ, allowing discrimination between 1O2 and free radical intermediacy. Of the two techniques described for analyzing Ch oxidation products, TLC with color development suffices for preliminary, mainly qualitative product screening, whereas a high-performance approach such as HPLC-EC(Hg) is advised when maximum resolution and sensitivity of quantitation are necessary. By using these strategies, one can monitor the formation of 1O2, for example, in a biologically relevant milieu (membrane), thus avoiding the difficulties associated with external detection, e.g., by physical means. These approaches would be valuable for assessing reaction mechanisms for various oxidative agents of biomedical importance, including environmental phototoxins and the rapidly emerging family of phototherapeutic drugs. Although photodynamic stress has been emphasized, the methods described should have broad applicability in the elucidation of oxidative mechanisms. |
| Cholesterol as a target for toxins de Kruijff, B. (1990), Biosci Rep 10(2): 127-30. Abstract: A mechanism is proposed for the way in which cholesterol facilitates channel formation by polyene antibiotics and bacterial protein toxins. Central elements of the model are: (i) interactions between the ring system of the sterol and rigid elements of the polyene or toxin molecule, and (ii) the specific orientation of cholesterol within the membrane. |
| Cholesterol as an aetiological agent in endodontic failures--a review Nair, P. N. (1999), Aust Endod J 25(1): 19-26. Abstract: Presence of cholesterol clefts in apical periodontitis lesions is a common histopathological observation. However, a potential aetiological association of cholesterol crystals to non-resolving apical periodontitis lesions after endodontic treatment has been suggested only recently. This article is an attempt to explain the biological basis for the inability of body cells to eliminate the local accumulation of cholesterol crystals, and to consolidate available clinical and experimental data in support of the view that massive accumulation of cholesterol crystals in inflamed periapical tissues can interfere with the periapical healing after conventional root canal treatment. As the irritating cholesterol crystals and certain other aetiological agents of failed endodontic treatment exist outside the root canal system, it is concluded that re-treatment alone, of such cases, is unlikely to resolve the factors that sustain the lesion. Apical surgery is indicated for successful management of such cases. |
| Cholesterol as an independent predictor of outcome after renal transplantation Roodnat, J. I., P. G. Mulder, et al. (2000), Transplantation 69(8): 1704-10. Abstract: BACKGROUND: The debate on the role of high serum cholesterol levels in cardiovascular disease or chronic vascular rejection in kidney-transplanted patients has not yet been settled. METHODS: We studied the influence of serum cholesterol at 1 year after transplantation on the failure risk in all 676 kidney graft recipients who survived with a functioning graft. Other variables included in this analysis were donor/recipient age and gender, original disease, race, number of HLA-A and -B mismatches, previous transplants, postmortal or living-related transplantation, and transplantation year. At 1 year after transplantation, we included: serum cholesterol, serum creatinine, proteinuria, and hypertension. RESULTS: In the Cox proportional hazards analysis, serum cholesterol at 1 year after transplantation turned out to be an important, independent variable influencing all end points (adjusted for all other variables in the model). The influence on graft failure censored for death was log-linear, and there was interaction with serum creatinine at 1 year. The adverse effect of elevated serum cholesterol levels on the graft failure rate decreased with increasing serum creatinine levels. The influence of serum cholesterol on the rate ratio (RR) for patient failure was linear too, and here there was interaction with recipient age. The negative influence of serum cholesterol on the RR for patient failure decreased with increasing recipient age. The risk for over-all graft failure was influenced by increasing serum cholesterol levels, and there was interaction with recipient age. Because recipient age had interaction with donor age and serum creatinine, the influence of all four variables together on the RR was estimated. It is shown that whereas the RR for over-all graft failure in young recipients of a renal transplant increases significantly with higher cholesterol levels, there is very little influence on the RR of elderly recipients. The risk increases proportionally with increasing serum creatinine levels. CONCLUSION: Serum cholesterol levels have an independent influence on graft, patient, and over-all graft failure. |
| Cholesterol as modulator of receptor function Gimpl, G., K. Burger, et al. (1997), Biochemistry 36(36): 10959-74. Abstract: The modulatory effect of cholesterol on the function of two structurally related peptide receptors, the oxytocin receptor and the brain cholecystokinin receptor in plasma membranes as well as in intact cells, was analyzed. Different approaches for cholesterol modification were applied: (i) depletion and reloading of cholesterol mediated by methyl-beta-cyclodextrin and cholesterol-methyl-beta-cyclodextrin, respectively, in a reversible manner; (ii) mild treatment of the plasma membranes with cholesterol oxidase under control of the membrane fluidity as measured by fluorescence anisotropy of diphenylhexatriene; and (iii) filipin pretreatment of membranes. The results allowed us to distinguish two mechanisms of cholesterol affecting the ligand-binding function of receptors: changes of the membrane fluidity as demonstrated for the cholecystokinin receptor, or a putatively specific cholesterol-receptor interaction as shown for the oxytocin receptor. This was confirmed in a structure-activity analysis with a variety of sterol analogues substituting for cholesterol in the membranes. While the agonist binding of the cholecystokinin receptor was supported by each of the tested steroids and was well correlated with the corresponding fluorescence anisotropy values, a stringent and unique requirement of the oxytocin receptor's affinity state for structural features of the sterol molecule was found. The molecular requirements differ both from those postulated for sterol-phospholipid interactions and from those known to be necessary for the functional activity of other proteins. The different behavior of both peptide receptors concerning the cholesterol dependence of their ligand binding was also present in vivo at the level of signal transduction. The results suggest that cholesterol can modulate receptor function by two distinct mechanisms, by changes of the membrane fluidity, and/or by a highly specific molecular interaction. |
| Cholesterol as stabilizer of the oxytocin receptor Gimpl, G. and F. Fahrenholz (2002), Biochim Biophys Acta 1564(2): 384-92. Abstract: The function of the oxytocin receptor system is strongly dependent on steroids as demonstrated by several physiological studies. One key element of this dependence on steroids may be the interaction of cholesterol and the oxytocin receptor. In this study, we show that cholesterol stabilizes the solubilized human oxytocin receptor against thermal inactivation and proteolytic degradation. In the absence of additional cholesterol, the soluble receptor inactivates within minutes. Maximal stabilization of the oxytocin receptor requires a continuous supply with cholesterol from a cholesterol-rich environment. A structure-activity analysis of various cholesterol analogues and their effect on the thermal stability of the oxytocin receptor showed that the stabilizing function of cholesterol was highly specific. The structural requirements of a potent stabilizing steroid are very similar to those necessary to support the high-affinity state of the receptor. Moreover, in the presence of cholesterol, the oxytocin receptor is significantly more stable against alterations of pH value (pH 4-12). The results show that cholesterol acts as a general stabilizer of the oxytocin receptor. |
| Cholesterol as target of Fe-NTA-induced lipid peroxidation in rat tissues Rosa, A., M. Deiana, et al. (2005), Toxicol Lett 157(1): 1-8. Abstract: Intraperitoneal injection of the iron-chelate, ferric-nitrilotriacetate (Fe-NTA), induces renal proximal tubular damage associated with oxidative damage in vivo. A sub-lethal dose of Fe-NTA (15 mg Fe/kg body weight) was administered IP to rats; animals were sacrificed and liver, kidney and plasma were collected 1-4 h after injection. In response to the Fe-NTA administration, there were significant time-dependent reductions of the levels of total lipids, cholesterol and total unsaturated fatty acids, and a rise in the concentrations of conjugated dienes, 7-ketocholesterol and fatty acids hydroperoxides, showing a pattern inversely correlated in plasma, kidney and liver. Cholesterol level decreased significantly from 1 h after injection in the kidney and 3-4 h in the plasma and liver of treated rats. This is the first report on cholesterol reduction and accumulated 7-ketocholesterol in the tissues of rats treated with Fe-NTA as a consequence of lipid peroxidation. |
| Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut Pereira, D. I. and G. R. Gibson (2002), Appl Environ Microbiol 68(9): 4689-93. Abstract: The objective of this study was to evaluate the effect of human gut-derived lactic acid bacteria and bifidobacteria on cholesterol levels in vitro. Continuous cultures inoculated with fecal material from healthy human volunteers with media supplemented with cholesterol and bile acids were used to enrich for potential cholesterol assimilators among the indigenous bacterial populations. Seven potential probiotics were found: Lactobacillus fermentum strains F53 and KC5b, Bifidobacterium infantis ATCC 15697, Streptococcus bovis ATCC 43143, Enterococcus durans DSM 20633, Enterococcus gallinarum, and Enterococcus faecalis. A comparative evaluation regarding the in vitro cholesterol reduction abilities of these strains along with commercial probiotics was undertaken. The degree of acid and bile tolerance of strains was also evaluated. The human isolate L. fermentum KC5b was able to maintain viability for 2 h at pH 2 and to grow in a medium with 4,000 mg of bile acids per liter. This strain was also able to remove a maximum of 14.8 mg of cholesterol per g (dry weight) of cells from the culture medium and therefore was regarded as a candidate probiotic. |
| Cholesterol at different bilayer concentrations can promote or antagonize lateral segregation of phospholipids of differing acyl chain length Silvius, J. R., D. del Giudice, et al. (1996), Biochemistry 35(48): 15198-208. Abstract: Fourier-transform infrared-spectroscopic and fluorescence measurements have been combined to examine the effect of cholesterol on the intermixing of short-chain dilauroyl phosphatidylcholine (DLPC) and its bromo-substituted derivative (12BrPC) with longer-chain (C16- or C18-) phosphatidylcholines (PCs) in hydrated lipid bilayers. Infrared spectroscopy of mixtures combining protonated DLPC or 12BrPC with chain-perdeuterated dipalmitoyl PC reveals that cholesterol at lower concentrations in the bilayer modifies the resolved thermal melting profiles for both phospholipid components and, at high bilayer concentrations, produces a convergence of the thermal transitions for the two PC species. Fluorescence-quenching measurements using a short-chain fluorescent PC (1-dodecanoyl-2-8-N-indolyloctanoyl PC) in ternary mixtures combining 12BrPC, dipalmitoyl or distearoyl PC, and cholesterol confirm that very high cholesterol levels (50 mol %) abolish the lateral segregation of the PC components at 25 degrees C, a temperature where the phospholipids extensively phase-separate in the absence of sterol. By contrast, under these same conditions cholesterol at lower concentrations in the bilayer is found to enhance the tendency of the PC components to exhibit lateral segregation. We show that these seemingly contradictory effects of cholesterol can be readily explained in the light of a ternary phase diagram that is fully consistent with out current understanding of the nature of cholesterol-phospholipid interactions in binary mixtures. |
| Cholesterol at the crossroads: Alzheimer's disease and lipid metabolism Wellington, C. L. (2004), Clin Genet 66(1): 1-16. Abstract: Alzheimer's Disease (AD) is a devastating disease that affects millions of elderly persons. Despite years of intense investigations, genetic risk factors that affect the majority of AD cases have yet to be determined. Recent studies suggest that cholesterol metabolism has integral part in AD pathogenesis, suggesting that genes that regulate lipid metabolism may also play roles in AD. This review will first describe emerging evidence that links cholesterol to the mechanisms thought to underlie AD. Based on this rationale, candidate genes located in regions implicated in AD that have roles in lipid metabolism will then be discussed. |
| Cholesterol atheroembolism: an increasingly frequent complication of cardiac catheterisation Ong, H. T., W. G. Elmsly, et al. (1991), Med J Aust 154(6): 412-4. Abstract: Cholesterol atheroembolisation is increasingly encountered as a complication of cardiac catheterisation. We report three cases seen recently in our unit. Autopsy and histological evidence confirmed cholesterol atheroembolism in one case, while the other two patients presented with classical clinical features of this condition. All three patients were elderly with extensive atheromatous disease. No excessive difficulty was encountered at catheterisation. Embolisation involved the gastrointestinal tract, the skin and extremities, and the kidneys. Despite anticoagulation, dialysis and surgical intervention all our patients died. With investigative and therapeutic catheterisation being increasingly performed in the setting of severe atherosclerosis, the need for continued scrutiny for catheter-induced complications is emphasised. |
| Cholesterol atheromatous embolism. The great masquerader revisited Lie, J. T. (1992), Pathol Annu 27 Pt 2: 17-50. |
| Cholesterol attenuates linoleic acid-induced endothelial cell activation Meerarani, P., E. J. Smart, et al. (2003), Metabolism 52(4): 493-500. Abstract: Vascular endothelial cell activation and dysfunction are critical early events in atherosclerosis. Even though very low or high levels of cholesterol can compromise cellular functions, cholesterol is a critical membrane component and may protect the vascular endothelium from oxidative stress and polyunsaturated fatty acid-mediated inflammatory responses. We have previously shown that the parent omega-6 fatty acid linoleic acid can markedly activate vascular endothelial cells. We now propose that membrane cholesterol can modify and inhibit linoleic acid-mediated endothelial cell dysfunction. To test this hypothesis, pulmonary artery endothelial cells were incubated with cholesterol (0 to 100 micromol/L) for 24 hours and then treated with 90 micromol/L of linoleic acid (18:2n-6) for 6 to 24 hours. In control cells, treatment with linoleic acid reduced intracellular glutathione levels and induced the DNA binding activity of nuclear factor-kappaB (NF-kappaB) leading to the upregulation of interleukin-6 (IL-6). In addition, the expression of endothelial nitric oxide synthase (eNOS) was altered, with linoleic acid increasing eNOS activity. In contrast, enrichment with cholesterol enhanced glutathione levels and reduced the linoleic acid-induced activation of NF-kappaBand the production of IL-6. Prior exposure to 50 micromol/L cholesterol also prevented the fatty acid-induced increase in eNOS activation. Cholesterol loading activated peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear receptor that can decrease inflammatory responses. Furthermore, the PPAR-gamma agonist thiazolidinedione markedly downregulated the NF-kappaB activation mediated by linoleic acid. Our data suggest that signaling pathways linked to endothelial cell activation by prooxidant and proinflammatory insults may be influenced by cellular cholesterol levels. |
| Cholesterol attenuates the interaction of the antimicrobial peptide gramicidin S with phospholipid bilayer membranes Prenner, E. J., R. N. Lewis, et al. (2001), Biochim Biophys Acta 1510(1-2): 83-92. Abstract: We have investigated the effect of the presence of 25 mol percent cholesterol on the interactions of the antimicrobial peptide gramicidin S (GS) with phosphatidylcholine and phosphatidylethanolamine model membrane systems using a variety of methods. Our circular dichroism spectroscopic measurements indicate that the incorporation of cholesterol into egg phosphatidylcholine vesicles has no significant effect on the conformation of the GS molecule but that this peptide resides in a range of intermediate polarity as compared to aqueous solution or an organic solvent. Our Fourier transform infrared spectroscopic measurements confirm these findings and demonstrate that in both cholesterol-containing and cholesterol-free dimyristoylphosphatidylcholine liquid-crystalline bilayers, GS is located in a region of intermediate polarity at the polar--nonpolar interfacial region of the lipid bilayer. However, GS appears to be located in a more polar environment nearer the bilayer surface when cholesterol is present. Our (31)P-nuclear magnetic resonance studies demonstrate that the presence of cholesterol markedly reduces the tendency of GS to induce the formation of inverted nonlamellar phases in model membranes composed of an unsaturated phosphatidylethanolamine. Finally, fluorescence dye leakage experiments indicate that cholesterol inhibits the GS-induced permeabilization of phosphatidylcholine vesicles. Thus in all respects the presence of cholesterol attenuates but does not abolish the interactions of GS with, and the characteristic effects of GS on, phospholipid bilayers. These findings may explain why it is more potent at disrupting cholesterol-free bacterial than cholesterol-containing eukaryotic membranes while nevertheless disrupting the integrity of the latter at higher peptide concentrations. This additional example of the lipid specificity of GS may aid in the rational design of GS analogs with increased antibacterial but reduced hemolytic activities. |
| Cholesterol attenuates the membrane perturbing properties of beta-amyloid peptides Kirsch, C., G. P. Eckert, et al. (2002), Amyloid 9(3): 149-59. Abstract: Growing evidence indicates a significant linkage between Abeta and cholesterol metabolism, although the exact role of cholesterol in brain aging and in the pathogenesis of AD is still unknown. Recently, in vitro and in vivo modification of cell cholesterol and its effect on Abeta-generation became a straight focus in the research of AD. In the present study, we discretely modulated the cholesterol contents of neuronal membranes from mice of different ages in vivo and in vitro using lovastatin and methyl-beta-cyclodextrin, respectively. The aim of the study was to investigate whether this modulation results in altered physico-chemical membrane properties. Therefore, we performed membrane fluidity measurements using three fluorescent dyes labeling different membrane regions. Furthermore, we evaluated the effects of cholesterol modulation on the membrane disturbing properties of Abeta. Modulation of membrane cholesterol content in vivo and in vitro was linked to changes in membrane properties. Very interestingly, cholesterol content of in vitro modulated neuronal membranes was negatively correlated with the membrane perturbing effects of Abeta. |
| Cholesterol autoantibody? Jakab, L. (1994), Orv Hetil 135(28): 1557. |