| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Large cholesterol polyps of the gallbladder: diagnosis by means of US and endoscopic US Sugiyama, M., Y. Atomi, et al. (1995), Radiology 196(2): 493-7. Abstract: PURPOSE: To identify ultrasonographic (US) features of large cholesterol polyps (> 10 mm in diameter) of the gallbladder in the differential diagnosis of polypoid lesions. MATERIALS AND METHODS: Sixty-seven patients underwent US (n = 67) and endoscopic US (n = 33). Fourteen patients had large cholesterol polyps. Findings in these patients were compared with those in patients with small cholesterol polyps (< or = 10 mm in diameter; n = 34) or other polypoid lesions (n = 19). RESULTS: US demonstrated the large cholesterol polyps as pedunculated masses with granular surfaces. In 94% of patients, all small cholesterol polyps were echogenic whereas the large cholesterol polyps tended to have decreased echogenicity. Endoscopic US showed complete or partial aggregation of echogenic spots in all cholesterol polyps-but not in other polypoid lesions, which included carcinomas. CONCLUSION: Aggregation of echogenic spots seems to be a US feature characteristic of both large and small cholesterol polyps. Routine use of endoscopic US is recommended for differential diagnosis of polypoid lesions because of its high resolution. |
| Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia Matsuzaki, M., T. Kita, et al. (2002), Circ J 66(12): 1087-95. Abstract: Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was > or =240 mg/dl and the average LDL-C concentration was > or =160 mg/dl. The incidence of coronary events increased in the patients with TG concentration > or =300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and >40 mg/dl for HDL-C. |
| Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT) Mabuchi, H., T. Kita, et al. (2002), Circ J 66(12): 1096-100. Abstract: Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively. |
| Large scale treatment? Limited knowledge about cholesterol and arteriosclerosis Berglund, G. (1991), Lakartidningen 88(19): 1762, 1764-5, 1767. |
| Large versus small unilamellar vesicles mediate reverse cholesterol transport in vivo into two distinct hepatic metabolic pools. Implications for the treatment of atherosclerosis Rodrigueza, W. V., K. D. Mazany, et al. (1997), Arterioscler Thromb Vasc Biol 17(10): 2132-9. Abstract: Phospholipid liposomes are synthetic mediators of "reverse" cholesterol transport from peripheral tissue to liver in vivo and can shrink atherosclerotic lesions in animals. Hepatic disposal of this cholesterol, however, has not been examined. We compared hepatic effects of large (approximately equal to 120-nm) and small (approximately equal to 35-nm) unilamellar vesicles (LUVs and SUVs), both of which mediate reverse cholesterol transport in vivo but were previously shown to be targeted to different cell types within the liver. On days 1, 3, and 5, rabbits were intravenously injected with 300 mg phosphatidylcholine (LUVs or SUVs) per kilogram body weight or with the equivalent volume of saline. After each injection, LUV- and SUV-injected animals showed large increases in plasma concentrations of unesterified cholesterol, indicating mobilization of tissue stores. After hepatic uptake of this cholesterol, however, SUV-treated animals developed persistently elevated plasma LDL concentrations, which by day 6 had increased to more than four times the values in saline-treated controls. In contrast, LUV-treated animals showed normal LDL levels. By RNase protection assay, SUVs suppressed hepatic LDL receptor mRNA at day 6 (to 61 +/- 4% of control, mean +/- SEM), whereas LUVs caused a statistically insignificant stimulation. Hepatic HMG-CoA reductase message was also significantly suppressed with SUV, but not LUV treatment, and hepatic 7 alpha-hydroxylase message showed a similar trend. These data on hepatic mRNA levels indicate that SUVs, but not LUVs, substantially perturbed liver cholesterol homeostasis. We conclude that LUVs and SUVs mobilize peripheral tissue cholesterol and deliver it to the liver, but to distinct metabolic pools that exert different regulatory effects. The effects of one of these artificial particles, SUVs, suggest that reverse cholesterol transport may not always be benign. In contrast, LUVs may be a suitable therapeutic agent, because they mobilize peripheral cholesterol to the liver without suppressing hepatic LDL receptor mRNA and without provoking a subsequent rise in plasma LDL levels. |
| Large-scale gene expression analysis of cholesterol dependence in NS0 cells Seth, G., R. J. Philp, et al. (2005), Biotechnol Bioeng 90(5): 552-67. Abstract: NS0, a nonsecreting mouse myeloma cell, is a major host line used for recombinant antibody production. These cells have a cholesterol-dependent phenotype and rely on an exogenous supply of cholesterol for their survival and growth. To better understand the physiology underlying cholesterol dependence, we compared NS0 cells, cultivated under standard cholesterol-dependent growth conditions (NS0), to cells adapted to cholesterol-independent conditions (NS0 revertant, NS0_r). Large-scale transcriptional analyses were done using the Affymetrix GeneChip array, MG-U74Av2. The transcripts expressed differentially across the two cell lines were identified. Additionally, proteomic tools were employed to analyze cell lysates from these two cell lines. Cellular proteins from both NS0 and NS0_r were subjected to 2D gel electrophoresis. MALDI-TOF mass spectrometry was performed to determine the identity of the differentially expressed spots. We examined the expression level of mouse genes directly involved in cholesterol biosynthesis, lipid metabolism, and central energy metabolism. Most of these genes were downregulated in the revertant cell type, NS0_r, compared to NS0. Overall, a large number of genes are expressed differentially, indicating that the reversal of cholesterol dependency has a profound effect on cell physiology. It is probable that a single gene mutation, activation, or inactivation is responsible for cholesterol auxotrophy. However, the wide-ranging changes in gene expression point to the distinct possibility of a regulatory event affecting the reversibility of auxotrophy, either directly or indirectly. |
| L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits Girerd, X. J., A. T. Hirsch, et al. (1990), Circ Res 67(6): 1301-8. Abstract: Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, for this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor synthesis. Accordingly, we designed a study to determine whether exogenous L-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra-arterial infusions of acetylcholine (0.3-9.0 micrograms/kg/min) and nitroprusside (0.3-9.0 micrograms/kg/min) were studied before and during intravenous administration of L-arginine (10 mg/kg/min), D-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. L-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. L-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor D-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous L-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits. |
| L-arginine restores cholesterol-attenuated microvascular responses in the rat cremaster Schuschke, D. A., F. N. Miller, et al. (1994), Int J Microcirc Clin Exp 14(4): 204-11. Abstract: The role of L-arginine in the reversal of cholesterol-induced endothelial dysfunction was studied in the cremaster muscle microcirculation. In vivo television microscopy was used to measure microvascular diameters and macromolecular leakage. Male Sprague-Dawley rats were fed either a normal chow diet or a diet supplemented with 1% cholesterol and 0.5% cholic acid for 3 weeks prior to in vivo experimentation. The cholesterol diet caused a decreased third-order arteriole dilator response to both acetylcholine and serotonin. This decreased responsiveness occurred in the presence of a higher plasma concentration of L-arginine and an increased ratio of L-arginine to its metabolite L-citrulline. The attenuation to both agonists was reversed by intravenous infusion of the nitric oxide precursor L-arginine (30-mg/kg bolus and 10-mg/kg/min continuous infusion). The cholesterol diet also decreased the postcapillary macromolecular leakage response to serotonin, and again this effect was reversed by L-arginine infusion. D-Arginine infusion had no restorative effect with either agonist in the cholesterol animals. Further experimentation with the nitric oxide production inhibitor N omega-nitro-L-arginine methyl ester demonstrated an inhibition of aretriolar dilation to acetylcholine, but there was no inhibition of dilation or macromolecular leakage to serotonin. Thus, it is probable that serotonin-induced leakage as well as dilation was not caused by stimulation of nitric oxide. These results suggest that L-arginine restores both nitric oxide-dependent and -independent dilation as well as macromolecular leakage in cholesterol-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Lasofoxifene (CP-336,156) protects against the age-related changes in bone mass, bone strength, and total serum cholesterol in intact aged male rats Ke, H. Z., H. Qi, et al. (2001), J Bone Miner Res 16(4): 765-73. Abstract: The purpose of this study was to evaluate if long-term (6 months) treatment with lasofoxifene (LAS), a new selective estrogen receptor modulator (SERM), can protect against age-related changes in bone mass and bone strength in intact aged male rats. Sprague-Dawley male rats at 15 months of age were treated (daily oral gavage) with either vehicle (n = 12) or LAS at 0.01 mg/kg per day (n = 12) or 0.1 mg/kg per day (n = 11) for 6 months. A group of 15 rats was necropsied at 15 months of age and served as basal controls. No significant change was found in body weight between basal and vehicle controls. However, an age-related increase in fat body mass (+42%) and decrease in lean body mass (-8.5%) was observed in controls. Compared with vehicle controls, LAS at both doses significantly decreased body weight and fat body mass but did not affect lean body mass. No significant difference was found in prostate wet weight among all groups. Total serum cholesterol was significantly decreased in all LAS-treated rats compared with both the basal and the vehicle controls. Both doses of LAS treatment completely prevented the age-related increase in serum osteocalcin. Peripheral quantitative computerized tomography (pQCT) analysis at the distal femoral metaphysis indicated that the age-related decrease in total density, trabecular density, and cortical thickness was completely prevented by treatment with LAS at 0.01 mg/kg per day or 0.1 mg/kg per day. Histomorphometric analysis of proximal tibial cancellous bone showed an age-related decrease in trabecular bone volume (TBV; -46%), trabecular number (Tb.N), wall thickness (W.Th), mineral apposition rate, and bone formation rate-tissue area referent. Moreover, an age-related increase in trabecular separation (Tb.Sp) and eroded surface was observed. LAS at 0.01 mg/kg per day or 0.1 mg/kg per day completely prevented these age-related changes in bone mass, bone structure, and bone turnover. Similarly, the age-related decrease in TBV and trabecular thickness (Tb.Th) and the age-related increase in osteoclast number (Oc.N) and osteoclast surface (Oc.S) in the third lumbar vertebral cancellous bone were completely prevented by treatment with LAS at both doses. Further, LAS at both doses completely prevented the age-related decrease in ultimate strength (-47%) and stiffness (-37%) of the fifth lumbar vertebral body. These results show that treatment with LAS for 6 months in male rats completely prevents the age-related decreases in bone mass and bone strength by inhibiting the increased bone resorption and bone turnover associated with aging. Further, LAS reduced total serum cholesterol and did not affect the prostate weight in these rats. Our data support the potential use of a SERM for protecting against the age-related changes in bone and serum cholesterol in elderly men. |
| Last comment on cholesterol Ravenskov, U. (1994), Lakartidningen 91(3): 117-8. |
| Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport Kobayashi, T., M. H. Beuchat, et al. (1999), Nat Cell Biol 1(2): 113-8. Abstract: The fate of free cholesterol released after endocytosis of low-density lipoproteins remains obscure. Here we report that late endosomes have a pivotal role in intracellular cholesterol transport. We find that in the genetic disease Niemann-Pick type C (NPC), and in drug-treated cells that mimic NPC, cholesterol accumulates in late endosomes and sorting of the lysosomal enzyme receptor is impaired. Our results show that the characteristic network of lysobisphosphatidic acid-rich membranes contained within multivesicular late endosomes regulates cholesterol transport, presumably by acting as a collection and distribution device. The results also suggest that similar endosomal defects accompany the anti-phospholipid syndrome and NPC. |
| Lateral diffusion in planar lipid bilayers: a fluorescence recovery after photobleaching investigation of its modulation by lipid composition, cholesterol, or alamethicin content and divalent cations Ladha, S., A. R. Mackie, et al. (1996), Biophys J 71(3): 1364-73. Abstract: In spite of the fact that planar lipid bilayers are still the best-suited artificial membrane system for the study of reconstituted ion channels and receptors, data dealing with their physical characterization, especially as regards dynamics, are scanty. A combined electrical and optical chamber was designed and allowed fluorescence recovery after photobleaching recovery curves to be recorded from stable virtually solvent-free bilayers. D, the lateral diffusion coefficient of N-(7-nitrobenzoyl-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn- glycero-3-phosphoethanolamine, was found to be relatively insensitive to the phospholipid composition (headgroup, chain unsaturation, etc.), whereas inclusion of 33-50% cholesterol in the membrane reduced D by a factor of 2. Divalent cations significantly reduced D of negatively charged bilayers. These results compare well with data gathered on other model and natural systems. In addition, the incorporation of the voltage-dependent pore-former alamethicin did slightly reduce lipid lateral mobility. This study demonstrates the feasibility of such experiments with planar bilayers, which are amenable to physical constraints, and thus offers new opportunities for systematic studies of structure-function relationships in membrane-associating molecules. |
| Lateral diffusion in the liquid phases of dimyristoylphosphatidylcholine/cholesterol lipid bilayers: a free volume analysis Almeida, P. F., W. L. Vaz, et al. (1992), Biochemistry 31(29): 6739-47. Abstract: The technique of fluorescence recovery after photobleaching is used to perform an extensive study of the lateral diffusion of a phospholipid probe in the binary mixture dimyristoylphosphatidylcholine/cholesterol, above the melting temperature of the phospholipid. In the regions of the phase diagram where a single liquid phase exists, diffusion can be quantitatively described by free volume theory, using a modified Macedo-Litovitz hybrid equation. In the liquid-liquid immiscibility region, the temperature dependence of the diffusion coefficient is in excellent agreement with current theories of generalized diffusivities in composite two-phase media. A consistent interpretation of the diffusion data can be provided based essentially on the idea that the primary effect of cholesterol addition to the bilayer is to occupy free volume. On this basis, a general interpretation of the phase behavior of this mixture is also proposed. |
| Lateral diffusion of cholesterol and dimyristoylphosphatidylcholine in a lipid bilayer measured by pulsed field gradient NMR spectroscopy Oradd, G., G. Lindblom, et al. (2002), Biophys J 83(5): 2702-4. Abstract: The pulsed field gradient NMR method for measuring self-diffusion has been used for a direct determination of the lateral diffusion coefficient of cholesterol, fluorine labeled at the 6-position, for an oriented lamellar liquid-crystalline phase of dimyristoylphosphatidylcholine (DMPC)/cholesterol/water. It is found that the diffusion coefficients of DMPC and cholesterol are equal over a large temperature interval. The apparent energy of activation for the diffusion process (58 kJ/mol) is about the same as for a lamellar phase of DMPC/water, whereas the phospholipid lateral diffusion coefficient is approximately four times smaller in the presence of cholesterol. |
| Lateral distribution of cholesterol in dioleoylphosphatidylcholine lipid bilayers: cholesterol-phospholipid interactions at high cholesterol limit Parker, A., K. Miles, et al. (2004), Biophys J 86(3): 1532-44. Abstract: Lateral organization of cholesterol in dioleoyl-phosphatidylcholine (DOPC) lipid bilayers at high cholesterol concentration (>45 mol%) was investigated using steady-state fluorescence anisotropy and fluorescent resonance energy transfer techniques. The recently devised Low Temperature Trap method was used to prepare compositionally uniform cholesterol/DOPC liposomes to avoid the problem of lipid demixing. The fluorescence anisotropy of diphenylhexatrience chain-labeled phosphatidylcholine (DPH-PC) in these liposomes exhibited local maxima at cholesterol mol fractions of 0.50 and 0.57, and a sharp drop at 0.67. For the liposomes labeled with both dehydroergosterol and DPH-PC, the fluorescent resonance energy transfer efficiency from dehydroergosterol to DPH-PC displayed a steep jump at cholesterol mol fraction of 0.5, and dips at 0.57 and 0.68. These results indicate the presence of highly ordered cholesterol regular distribution domains at those observed critical compositions. The observed critical mol fraction at 0.67 agreed favorably with the solubility limit of cholesterol in DOPC bilayers as independently measured by light scattering and optical microscopy. The regular distribution at 0.57 was previously predicted from a Monte Carlo simulation based on the Umbrella model. The results strongly support the hypothesis that the primary requirement for cholesterol-phospholipid mixing is that the polar phospholipid headgroups need to cover the nonpolar body of cholesterol to avoid the exposure of cholesterol to water. |
| Lateral distribution of cholesterol in membranes probed by means of a pyrene-labelled cholesterol: effects of acyl chain unsaturation Lagane, B., S. Mazeres, et al. (2002), Biophys Chem 95(1): 7-22. Abstract: The lateral distribution of cholesterol in membranes in the fluid state was investigated by studying the variation of the molar absorption coefficient of pyrene-labelled cholesterol (Py-chol) vs. its concentration in vesicles made of phosphatidylcholine, with variable acyl chain unsaturations. Absorption measurements indicated non-ideal mixing of Py-chol in unsaturated lipids, a process mainly controlled by the cholesterol moiety of the probe. Similar abilities of cholesterol and Py-chol in perturbing the phase properties of pure saturated phosphatidylcholine were observed by DSC experiments. Immiscibility of sterols was corroborated by fluorescence polarization measurements, which indicated a weaker ordering effect of cholesterol in unsaturated membranes. The sizes and the quantities of sterol oligomers formed were calculated. A model for the lateral distribution of cholesterol in membranes is proposed and is applied to known cholesterol/phosphatidylcholine phase diagrams. Finally, the results are discussed with regard to recent models of biological membrane organization, (i.e. rafts). |
| Lateral domain formation in cholesterol/phospholipid monolayers as affected by the sterol side chain conformation Mattjus, P., R. Bittman, et al. (1995), Biochim Biophys Acta 1240(2): 237-47. Abstract: The interaction of side-chain variable cholesterol analogues with dipalmitoylphosphatidylcholine (DPPC) or N-palmitoylsphingomyelin (N-PSPM) has been examined in monolayer membranes at the air/water interface. The sterols had either unbranched (n-series) or single methyl-branched (iso-series) side chains, with the length varying between 3 and 10 carbons (C3-C10). The efficacy of interaction between the sterols and the phospholipids was evaluated based on the ability of the sterols to form condensed sterol/phospholipid domains in the phospholipid monolayers. Domain formation was detected with monolayer fluorescence microscopy using NBD-cholesterol as the fluorescent probe. In general, a side chain length of at least 5 carbons was necessary for the unbranched sterols to form visible sterol/phospholipid domains in DPPC or N-PSPM mixed monolayers. With the iso-analogues, a side chain of at least 6 carbons was needed for sterol/phospholipid domains to form. The macroscopic domains were stable up to a certain surface pressure (ranging from 1 to 12 mN/m). At this onset phase transformation pressure, the domain line boundary dissipated, and the monolayer entered into an apparent one phase state (no clearly visible lateral domains). However, with some DPPC monolayers containing short chain sterols (n-C3, n-C4,n-C5, and i-C5), a new condensed phase appeared to form (at 20 mol%) when the monolayer was compressed beyond the phase transformation pressure. These precipitates formed at surface pressures between 6-8.3 mN/m, were clearly observable up to at least 30 mN/m. When the monolayers containing these four sterols were allowed to expand, the condensed precipitates dissolved at the same pressure at which they were formed during monolayer compression. No condensed precipitates were observed with these sterols in corresponding N-PSPM monolayers. Taken together, the results of this study emphasize the importance of the length and conformation of the cholesterol side chain in determining the efficacy of sterol/phospholipid interaction in model membranes. The major difference between DPPC and N-PSPM monolayers at different sterol compositions was mainly the lateral distribution and the size of the domains as well as the onset phase transformation pressure intervals. |
| Lateral domain formation in mixed monolayers containing cholesterol and dipalmitoylphosphatidylcholine or N-palmitoylsphingomyelin Slotte, J. P. (1995), Biochim Biophys Acta 1235(2): 419-27. Abstract: Epifluorescence microscopy was used to visualize the formation of lateral fluid domains in monolayers of dipalmitoylphosphatidylcholine (DPPC) or N-palmitoylsphingomyelin (N-P-SM) containing cholesterol. NBD-Cholesterol was used as a fluorophore at 1 mol%. Image analysis of the monolayer surface texture (taken during the first compression at 22 degrees C and 1.5 mN/m) showed that the area of the liquid-condensed domains increased (from zero to 90% of the total area) with increasing cholesterol concentration (5 to 40 mol%), both in DPPC and N-P-SM mixed monolayers. The liquid-condensed domains had a significantly larger size in DPPC than in N-P-SM monolayers, but were more numerous in N-P-SM monolayers. Lateral domain boundary lines begun to dissipate at a certain surface pressure. This characteristic phase transformation pressure was markedly higher in N-P-SM (3-12 mN/m) than in DPPC mixed monolayers (1.8-3.7 mN/m), and also increased with increasing cholesterol concentration. If a monolayer was first compressed above the phase transformation pressure (to 15 mN/m), and then expanded to a lateral surface pressure of 1.5 mN/m, the liquid-condensed domains coalesced if the cholesterol concentrations was 25 mol% or higher (both DPPC and N-P-SM monolayers). In conclusion, the cholesterol/DPPC and cholesterol/N-P-SM interactions in the monolayers appeared to differ to a large extent, since the liquid-condensed domains in the two systems differed in number, size, and properties. Differences in molecular properties were reflected in the phase transformation pressures, which were markedly higher in cholesterol/N-P-SM monolayers as compared to cholesterol/DPPC membranes. |
| Lateral domain heterogeneity in cholesterol/phosphatidylcholine monolayers as a function of cholesterol concentration and phosphatidylcholine acyl chain length Slotte, J. P. (1995), Biochim Biophys Acta 1238(2): 118-26. Abstract: Mixed monolayers of cholesterol and phosphatidylcholines having symmetric, different length acyl chains (10 to 16 carbons each) were prepared at the air/water interface. The partitioning of a fluorescent probe, NBD-cholesterol at 0.5 mol%, among lateral domains was determined by epifluorescence microscopy. The mixed monolayers had cholesterol concentrations of 20, 25, or 33 mol%, and in all these monolayers, lateral domain heterogeneity was observed within a defined surface pressure interval. This surface pressure interval was highly influenced by the phosphatidylcholine acyl chain length, but not by the cholesterol content of the mixed monolayer. The characteristic surface pressure, at which the line boundary between expanded and condensed phases dissolved (phase transformation pressure), and the monolayer entered an apparent phase-miscible state, was about 20 mN/m for di10PC and decreased as a linear function of the phosphatidylcholine acyl chain length to be about 2.5 mN/m for di16PC. During initial compression of the monolayers, the sizes of the condensed phases were generally larger, and to some extent heterogeneous with respect to the size distribution, as compared to the situation in monolayers which had experienced a compression/expansion cycle, which took them above the phase transformation pressure. This suggest that the domains observed during initial compression were not equilibrium structures. This study has demonstrated that both the cholesterol content and the phosphatidylcholine acyl chain length markedly influenced the properties of laterally condensed domains in these mixed monolayers. Since the possibility for the formation of attractive van der Waals forces between cholesterol and acyl chains increase with increasing acyl chain length, and since the phosphocholine head group is similar in all systems examined, the observed differences in domain shapes, properties, and stability most likely resulted from differences in van der Waals forces. |
| Lateral interactions of pig apolipoprotein A-1 with egg yolk phosphatidylcholine and with cholesterol in mixed monolayers at the triolein-saline interface Handa, T., H. Saito, et al. (1992), Biochemistry 31(5): 1415-20. Abstract: Interfacial tensions of egg yolk phosphatidylcholine (PC) and cholesterol monolayers adsorbed at the triolein-saline interface were measured in the presence and absence of pig apolipoprotein A-1 (apoA-1) in the saline phase. In the absence of apoA-1, the adsorptions of PC and cholesterol at the interface from the triolein phase are cooperative, showing large lateral attractive interactions between the PC molecules and the cholesterol molecules in the monolayer. In the presence of apoA-1, the PC adsorption is anti-cooperative, indicating strong lateral attractive interactions between the PC and the apoA-1 molecules, i.e., apparently, repulsive lateral interactions between the PC molecules. On the other hand, lateral interactions of very low magnitude are observed between the cholesterol and apoA-1 molecules in the monolayer. Values of the lateral interaction energy are evaluated from the adsorption data by the Defay-Prigogine-Flory theory of monolayers. The large difference in lateral interaction energy with apoA-1 between PC and cholesterol in a mixed monolayer is discussed in connection with current problems in lipoprotein catabolism: reverse cholesterol transport, alterations in affinity of lipid particles to apoA-1, and formation of high-density lipoproteins and abnormal lipoproteins. |