共查询到20条相似文献，搜索用时 15 毫秒
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Aouizerat BE Engler MB Natanzon Y Kulkarni M Song J Eng C Huuskonen J Rivera C Poon A Bensley M Sehnert A Zellner C Malloy M Kane J Pullinger CR 《Journal of lipid research》2006,47(4):787-793
Phospholipid transfer protein (PLTP) participates in key processes in lipoprotein metabolism, including interparticle phospholipid transfer, remodeling of HDL, cholesterol and phospholipid efflux from peripheral tissues, and the production of hepatic VLDL. The impact of PLTP on reverse cholesterol transport suggests that the gene may harbor sequence anomalies that contribute to disorders of HDL metabolism. The human PLTP gene was screened for sequence anomalies by DNA melting analysis in 276 subjects with hypoalphalipoproteinemia (HA) and 364 controls. The association with plasma lipid parameters was evaluated. We discovered 18 sequence variations, including four missense mutations and a novel polymorphism (c.-34G > C). In healthy controls, the c.-34G > C minor allele was associated with higher high density lipoprotein-cholesterol (HDL-C) and was depleted in subjects with HA. Linear regression models predict that possession of the rare allele decreases plasma triglyceride (TG) and TG/HDL-C and increases HDL-C independent of TG. Decreased PLTP activity was observed in one (p.R235W) of four (p.E72G, p.S119A, p.S124Y, and p.R235W) mutations in an in vitro activity assay. These findings indicate that PLTP gene variation is an important determinant of plasma lipoproteins and affects disorders of HDL metabolism. 相似文献
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Kohtaro Asayama Hidemasa Hayashibe Kazushige Dobashi Norihiko Uchida Takaya Nakane Kohji Kodera Akira Shirahata 《Obesity (Silver Spring, Md.)》2002,10(6):439-446
Objective: To determine whether serum cholesteryl ester transfer protein (CETP), which is one of the physiologically active gene products secreted from adipose tissue, is increased and associated with atherogenic lipoprotein profile in obese children. Research Methods and Procedures: Subjects were 42 consecutive outpatient Japanese obese children, 29 boys and 13 girls, ranging in age from 5 to 14 years, and 25 age‐matched non‐obese children, 13 boys and 12 girls, as the control group for measuring CETP mass. Blood was drawn after an overnight fast and, at the same time, and anthropometric measurements including height, body weight, waist girth, hip girth, and triceps and subscapular skinfold thicknesses were taken. Paired samples were obtained from 15 obese children who underwent psychoeducational therapy. Serum CETP mass was assayed by an enzyme‐linked immunosorbent assay. Results: The serum levels of triglyceride, total cholesterol (TC), low‐density lipoprotein cholesterol, TC/high‐density lipoprotein cholesterol (HDLC), apolipoproteins (apo) B, apo B/apo A1, and insulin in obese children were significantly higher than the respective reference values. Serum CETP level was ～2‐fold higher (98.7 ± 3.6 vs. 50.9 ± 4.0 nM, means ± SEM, p < 0.001) in the obese children than in the controls. In 15 obese children, whose percentage of overweight declined during therapy, CETP levels decreased significantly. CETP level was correlated with HDLC, TC/HDLC, and insulin, and with percentage of overweight when the data of the obese and non‐obese children were combined. Discussion: CETP is increased and associated with the atherogenic lipoprotein profile in obese children. 相似文献
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Philip J. Barter Kerry-Anne Rye Mohan S. Beltangady William C. Ports William T. Duggan S. Matthijs Boekholdt David A. DeMicco John J. P. Kastelein Charles L. Shear 《Journal of lipid research》2012,53(11):2436-2442
Development of the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, was halted after the ILLUMINATE trial revealed an increase in both all-cause mortality (ACM) and major cardiovascular events (MCVEs) associated with its use. We now report that the harm caused by torcetrapib was confined to those in the 10 mg atorvastatin subgroup for both ACM [hazard ratio (HR) = 2.68, 95% CI (1.58, 4.54), P < 0.0001] and MCVEs [HR = 1.41, 95% CI (1.14, 1.74), P = 0.002], with no evidence of harm when torcetrapib was coadministered with higher doses of atorvastatin. In the atorvastatin 10 mg subgroup, age, prior heart failure and stroke were significantly associated with ACM, independent of torcetrapib treatment, whereas low apoA-I, smoking, hypertension, heart failure, myocardial infarction, and stroke were independently associated with MCVEs. After adjusting for these factors, the HR associated with torcetrapib treatment in the 10 mg atorvastatin subgroup remained elevated for both ACM [HR = 2.67, 95% CI (1.57, 4.54), P < 0.001] and MCVE [HR = 1.36, 95% CI (1.10, 1.69), P = 0.005]. Thus, the harm caused by torcetrapib was confined to individuals taking atorvastatin 10 mg. The harm could not be explained by torcetrapib-induced changes in lipid levels, blood pressure, or electrolytes. It is conceivable that higher doses of atorvastatin protected against the harm caused by torcetrapib. 相似文献
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Systemic phospholipid transfer protein (PLTP) is a recognized risk factor for coronary heart disease. In apolipoprotein E-deficient mice, systemic PLTP deficiency is atheroprotective, whereas PLTP overexpression is proatherogenic. As expected, we also observed significantly smaller lesions (P < 0.0001) in hypercholesterolemic double mutant low density lipoprotein receptor-deficient (LDLr(-/-)) PLTP-deficient (PLTP(-/-)) mice compared with LDLr(-/-) mice expressing systemic PLTP. To assess the specific contribution of only macrophage-derived PLTP to atherosclerosis progression, bone marrow transplantation was performed in LDLr(-/-) mice that also lacked systemic PLTP. Groups of double mutant PLTP(-/-)LDLr(-/-) mice were irradiated with 1,000 rad and injected with bone marrow (BM) cells collected from either PLTP(-/-) or wild-type mice. When fed a high-fat diet, BM cell expression of PLTP decreased plasma cholesterol of PLTP(-/-)LDLr(-/-) mice from 878 +/- 220 to 617 +/- 183 mg/dl and increased HDL cholesterol levels from 54 +/- 11 to 117 +/- 19 mg/dl. This decreased total plasma cholesterol and increased HDL cholesterol contributed to the significantly smaller atherosclerotic lesions in both aortas and heart sinus valves observed in these mice. Thus, unlike total systemic PLTP, locally produced macrophage-derived PLTP beneficially alters lipoprotein metabolism and reduces lesion progression in hyperlipidemic mice. 相似文献
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Siggins S Kärkkäinen M Tenhunen J Metso J Tahvanainen E Olkkonen VM Jauhiainen M Ehnholm C 《Journal of lipid research》2004,45(2):387-395
Human plasma contains two forms of phospholipid transfer protein (PLTP), one catalytically active [high-activity PLTP (HA-PLTP)] and the other a low-activity (LA-PLTP) form. We present here a PLTP ELISA that allows not only for accurate measurement of PLTP concentration in plasma but also of the distribution of both LA- and HA-PLTP. To achieve similar immunoreactivity of the two PLTP forms, a denaturing sample pretreatment with 0.5% SDS was required. Distribution of LA- and HA-PLTP in plasma was assessed using size-exclusion chromatography, Heparin-Sepharose chromatography, anti-PLTP immunoaffinity chromatography, and dextran sulfate-CaCl2 precipitation. All four methods demonstrated that approximately 60% of plasma PLTP represents LA-PLTP and 40% represents HA-PLTP. According to the modified ELISA, the total serum PLTP concentration in a random Finnish population sample (n = 80) was 5.81 +/- 1.33 mg/l (mean +/- SD) (range, 2.78-10.06 mg/l) and the mean activity was 5.84 +/- 1.39 micromol/ml/h (range, 3.21-11.15 micromol/ml/h). To quantitate both forms of PLTP in sera from this sample, we combined dextran sulfate-CaCl2 precipitation with the modified PLTP ELISA. The HA-PLTP mass (mean, 1.87 +/- 0.85 mg/l) correlated significantly with serum PLTP activity, whereas that of LA-PLTP (mean, 3.94 +/- 1.4 mg/l) showed no correlation with phospholipid transfer activity. 相似文献
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Geraldine Cilpa-Karhu Matti Jauhiainen Marja-Liisa Riekkola 《Journal of lipid research》2015,56(1):98-108
Inhibition of cholesterol ester transfer protein (CETP), a protein mediating transfer of neutral lipids between lipoproteins, has been proposed as a means to elevate atheroprotective HDL subpopulations and thereby reduce atherosclerosis. However, off-target and adverse effects of the inhibition have raised doubts about the molecular mechanism of CETP-HDL interaction. Recent experimental findings have demonstrated the penetration of CETP into HDL. However, atomic level resolution of CETP penetration into HDL, a prerequisite for a better understanding of CETP functionality and HDL atheroprotection, is missing. We constructed an HDL particle that mimics the actual human HDL mass composition and investigated for the first time, by large-scale atomistic molecular dynamics, the interaction of an upright CETP with a human HDL-mimicking model. The results demonstrated how CETP can penetrate the HDL particle surface, with the formation of an opening in the N barrel domain end of CETP, put in evidence the major anchoring role of a tryptophan-rich region of this domain, and unveiled the presence of a phenylalanine barrier controlling further access of HDL-derived lipids to the tunnel of CETP. The findings reveal novel atomistic details of the CETP-HDL interaction mechanism and can provide new insight into therapeutic strategies. 相似文献
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We reported that phospholipid transfer protein (PLTP) deficiency decreased atherosclerosis in mouse models. Because the decreased atherosclerosis was accompanied by a significant decrease in plasma HDL levels, we examined the properties of PLTP knockout (PLTP0) HDL and tested its ability to prevent LDL-induced monocyte chemotactic activity in human artery wall cell cocultures. We isolated HDL and LDL from LDL receptor knockout/PLTP knockout (LDLr0/PLTP0) mice and from apolipoprotein B transgenic (apoBTg)/PLTP0 mice as well as their controls. PLTP0 HDL was relatively rich in protein and depleted in phosphatidylcholine. Turnover studies revealed a 3.5- to 4.0-fold increase in the turnover of protein and cholesteryl ester in HDL from PLTP0 mice compared with control mice. The ability of HDL from LDLr0/PLTP0 and apoBTg/PLTP0 mice to prevent the induction of monocyte chemotactic activity in human artery wall cell cocultures exposed to human LDL was dramatically better than that in controls. Moreover, LDL from PLTP0 mice was markedly resistant to oxidation and induced significantly less monocyte chemotactic activity compared with that in controls. In vitro, PLTP0 HDL removed significantly more oxidized phospholipids from LDL than did control HDL. We conclude that PLTP deficiency improves the anti-inflammatory properties of HDL in mice and reduces the ability of LDL to induce monocyte chemotactic activity. 相似文献
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Mulya A Lee JY Gebre AK Boudyguina EY Chung SK Smith TL Colvin PL Jiang XC Parks JS 《Journal of lipid research》2008,49(11):2390-2401
We investigated the in vivo metabolic fate of pre-beta HDL particles in human apolipoprotein A-I transgenic (hA-I (Tg)) mice. Pre-beta HDL tracers were assembled by incubation of [(125)I]tyramine cellobiose-labeled apolipoprotein A-I (apoA-I) with HEK293 cells expressing ABCA1. Radiolabeled pre-beta HDLs of increasing size (pre-beta1, -2, -3, and -4 HDLs) were isolated by fast-protein liquid chromatography and injected into hA-I (Tg)-recipient mice, after which plasma decay, in vivo remodeling, and tissue uptake were monitored. Pre-beta2, -3, and -4 had similar plasma die-away rates, whereas pre-beta1 HDL was removed 7-fold more rapidly. Radiolabel recovered in liver and kidney 24 h after tracer injection suggested increased (P < 0.001) liver and decreased kidney catabolism as pre-beta HDL size increased. In plasma, pre-beta1 and -2 were rapidly (<5 min) remodeled into larger HDLs, whereas pre-beta3 and -4 were remodeled into smaller HDLs. Pre-beta HDLs were similarly remodeled in vitro with control or LCAT-immunodepleted plasma, but not when incubated with phospholipid transfer protein knockout plasma. Our results suggest that initial interaction of apoA-I with ABCA1 imparts a unique conformation that partially determines the in vivo metabolic fate of apoA-I, resulting in increased liver and decreased kidney catabolism as pre-beta HDL particle size increases. 相似文献
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Moerland M Samyn H van Gent T Jauhiainen M Metso J van Haperen R Grosveld F van Tol A de Crom R 《Journal of lipid research》2007,48(12):2622-2631
In low density lipoprotein receptor (LDLR)-deficient mice, overexpression of human plasma phospholipid transfer protein (PLTP) results in increased atherosclerosis. PLTP strongly decreases HDL levels and might alter the antiatherogenic properties of HDL particles. To study the potential interaction between human PLTP and apolipoprotein A-I (apoA-I), double transgenic animals (hPLTPtg/hApoAItg) were compared with hApoAItg mice. PLTP activity was increased 4.5-fold. Plasma total cholesterol and phospholipid were decreased. Average HDL size (analyzed by gel filtration) increased strongly, hPLTPtg/hApoAItg mice having very large, LDL-sized, HDL particles. Also, after density gradient ultracentrifugation, a substantial part of the apoA-I-containing lipoproteins in hPLTPtg/hApoAItg mice was found in the LDL density range. In cholesterol efflux studies from macrophages, HDL isolated from hPLTPtg/hApoAItg mice was less efficient than HDL isolated from hApoAItg mice. Furthermore, it was found that the largest subfraction of the HDL particles present in hPLTPtg/hApoAItg mice was markedly inferior as a cholesterol acceptor, as no labeled cholesterol was transferred to this fraction. In an LDLR-deficient background, the human PLTP-expressing mouse line showed a 2.2-fold increased atherosclerotic lesion area. These data demonstrate that the action of human PLTP in the presence of human apoA-I results in the formation of a dysfunctional HDL subfraction, which is less efficient in the uptake of cholesterol from cholesterol-laden macrophages. 相似文献
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Copper-induced LDL oxidation is characterized by an 'induction phase' (lag phase) during which the endogenous antioxidants are consumed, followed by a 'propagation phase' in which the LDL-associated polyunsaturated fatty acids are oxidized. Oxidation products may play an important role in the propagation of the oxidative process in the arterial intima as they increase the permeability of the damaged endothelium to various plasma components, including LDL. We therefore found it of interest to investigate the kinetics of LDL oxidation in vitro under conditions where LDL is sequentially exposed to Cu2+-induced oxidation.
The results of our studies demonstrate that when native LDL is exposed to copper oxidation in a medium containing oxidized LDL, oxidation of the added LDL may be almost instantaneous. Furthermore, even when native LDL is added to 'oxidizing LDL' towards the end of the lag phase or during the propagation phase it becomes oxidized after a very short lag. This oxidation process, occurring in spite of the possible protective effect of the antioxidants present in the newly added LDL, indicates that although antioxidants prolong the latency period by preventing the formation of active free radicals, when such radicals are present in the system, oxidation propagates. These results lend strong support to the generally accepted paradigm regarding the mechanism of propagation of lipid oxidation.
In view of the effect of oxidation products on the permeability of the endothelium, the observed shortening of the lag period may result in a vicious cycle, independent of the LDL-associated antioxidants, leading to continuing oxidation and foam cell formation. 相似文献
The results of our studies demonstrate that when native LDL is exposed to copper oxidation in a medium containing oxidized LDL, oxidation of the added LDL may be almost instantaneous. Furthermore, even when native LDL is added to 'oxidizing LDL' towards the end of the lag phase or during the propagation phase it becomes oxidized after a very short lag. This oxidation process, occurring in spite of the possible protective effect of the antioxidants present in the newly added LDL, indicates that although antioxidants prolong the latency period by preventing the formation of active free radicals, when such radicals are present in the system, oxidation propagates. These results lend strong support to the generally accepted paradigm regarding the mechanism of propagation of lipid oxidation.
In view of the effect of oxidation products on the permeability of the endothelium, the observed shortening of the lag period may result in a vicious cycle, independent of the LDL-associated antioxidants, leading to continuing oxidation and foam cell formation. 相似文献
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Nakanishi S Vikstedt R Söderlund S Lee-Rueckert M Hiukka A Ehnholm C Muilu M Metso J Naukkarinen J Palotie L Kovanen PT Jauhiainen M Taskinen MR 《Journal of lipid research》2009,50(2):183-192
The main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL < or =10(th) and HDL > or =90(th) Finnish age/sex-specific percentile. Cholesterol efflux from [(3)H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I (apoA-I), HDL(2), and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera (0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL(2), and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low-HDL subjects (P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB (P = 0.033), apoA-I (P = 0.004), apoA-II (P < 0.0001), and the percentage of apoA-I present in the form of prebeta-HDL (P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects. 相似文献
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Daniel Seung Kim Amber A. Burt Jane E. Ranchalis Simona Vuletic Tomas Vaisar Wan-Fen Li Elisabeth A. Rosenthal Weijiang Dong Jason F. Eintracht Arno G. Motulsky John D. Brunzell John J. Albers Clement E. Furlong Gail P. Jarvik 《Journal of lipid research》2015,56(7):1351-1362
Recent studies have failed to demonstrate a causal cardioprotective effect of HDL cholesterol levels, shifting focus to the functional aspects of HDL. Phospholipid transfer protein (PLTP) is an HDL-associated protein involved in reverse cholesterol transport. This study sought to determine the genetic and nongenetic predictors of plasma PLTP activity (PLTPa), and separately, to determine whether PLTPa predicted carotid artery disease (CAAD). PLTPa was measured in 1,115 European ancestry participants from a case-control study of CAAD. A multivariate logistic regression model was used to elucidate the relationship between PLTPa and CAAD. Separately, a stepwise linear regression determined the nongenetic clinical and laboratory characteristics that best predicted PLTPa. A final stepwise regression considering both nongenetic and genetic variables identified the combination of covariates that explained maximal PLTPa variance. PLTPa was significantly associated with CAAD (7.90 × 10−9), with a 9% decrease in odds of CAAD per 1 unit increase in PLTPa (odds ratio = 0.91). Triglyceride levels (P = 0.0042), diabetes (P = 7.28 × 10−5), paraoxonase 1 (PON1) activity (P = 0.019), statin use (P = 0.026), PLTP SNP rs4810479 (P = 6.38 × 10−7), and PCIF1 SNP rs181914932 (P = 0.041) were all significantly associated with PLTPa. PLTPa is significantly inversely correlated with CAAD. Furthermore, we report a novel association between PLTPa and PON1 activity, a known predictor of CAAD. 相似文献
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《Animal : an international journal of animal bioscience》2015,9(6):1000-1007
A high-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its potential atherogenic effect. Increasingly often, humans spend periods/days eating in a completely unregulated way, ingesting excessive amounts of food rich in oils and fats, alternating with periods/days when food intake is more or less correct. We investigate the effect on lipid homeostasis of a high-fat diet administered either continuously or intermittently. We investigated control pigs receiving standard diet (C, n=7), pigs receiving a high-fat diet every day for 10 weeks (CHF, n=5), and pigs receiving a high-fat diet every other week for 10 weeks (IHF, n=7). IHF animals were shown to have a different lipid profile compared with CHF animals, with a significant increase in high-density lipoproteins (HDL) levels with respect to C and CHF groups. CHF also showed significantly higher values of TC/HDL cholesterol compared with C and IHF. Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα along with its target genes in the CHF group and in the IHF group, whereas SREBP2 and LDLr were significantly inhibited. A significant correlation was found between ABCA1 expression and circulating levels of HDL-C. Periodic withdrawals of a high-fat atherogenic diet compared with a regular administration results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL-C and lower TC/HDL-C. 相似文献
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D. Michael Hallman Spencer A. Brown Christie M. Ballantyne A. Richey Sharrett Eric Boerwinkle 《Biomarkers》2004,9(2):190-202
Low-density lipoprotein (LDL) particle size has been associated with coronary heart disease, but an association between LDL size and preclinical atherosclerosis is less well established. Using gradient gel electrophoresis, large (A), intermediate (I) and small (B) LDL size subclasses were determined in 198 cases with asymptomatic carotid artery atherosclerosis (determined by B-mode ultrasonography) and 318 controls from the Atherosclerosis Risk in Communities (ARIC) Study. In Caucasians, a smaller LDL size was more prevalent in men and associated with a higher body mass index, hypertension prevalence, and plasma total- and LDL-cholesterol and triglycerides, but lower HDL-cholesterol. In African-Americans, a smaller LDL size was associated with higher triglycerides and lower HDL-cholesterol and hypertension prevalence. In Caucasians, Subclass B prevalence was 29.1% among cases and 14.8% among controls. The odds ratio (95% confidence interval) for Subclass B rather than Subclass A in Caucasian cases was 2.94 (1.67-5.17); the association remained significant after controlling for age, body mass index, smoking, and either plasma triglycerides or HDL-cholesterol. In African-Americans, however, there was no significant association between LDL subclass and case status. A predominance of smaller LDL particles is associated with asymptomatic carotid artery atherosclerosis in Caucasians, through mechanisms that remain to be elucidated. 相似文献
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Calabresi L Baldassarre D Simonelli S Gomaraschi M Amato M Castelnuovo S Frigerio B Ravani A Sansaro D Kauhanen J Rauramaa R de Faire U Hamsten A Smit AJ Mannarino E Humphries SE Giral P Veglia F Sirtori CR Franceschini G Tremoli E 《Journal of lipid research》2011,52(8):1569-1574
Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (P=0.30 and P=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (P for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis. 相似文献
19.
Marsh D 《Protein science : a publication of the Protein Society》2003,12(9):2109-2117
Dihedral angles are evaluated for the phospholipid ligands of the lipid-binding proteins found in the Protein Data Base (PDB). Phospholipid structures occur with a trans C1-C2 configuration of the glycerol backbone and oppositely extended chains, in addition to the gauche C1-C2 rotamers found in membranes. Headgroup conformations are not restricted to the single bent-down configuration and gauche-gauche configuration of the phosphodiester that is found in phospholipid crystals. Additionally, fully extended headgroups and orientations directed away from the lipid chains are found for phospholipids in the protein binding pockets. On average, the hydrocarbon chains of the protein-bound lipids are conformationally more disordered than in fluid bilayer membranes. However, much of this configurational disorder arises from energetically disallowed skew conformations. This suggests a configurational heterogeneity in the lipids at a single binding site: Eclipsed conformations occur also in some lipid headgroups and glycerol backbones. Stereochemical violations appear for some of the ester carboxyl groups of the protein-bound phospholipids in the PDB, and two glycerol backbones have the incorrect enantiomeric configuration. 相似文献
20.
D. Michael Hallman Spencer A. Brown Christie M. Ballantyne A. Richey Sharrett Eric Boerwinkle 《Biomarkers》2013,18(2):190-202
Low-density lipoprotein (LDL) particle size has been associated with coronary heart disease, but an association between LDL size and preclinical atherosclerosis is less well established. Using gradient gel electrophoresis, large (A), intermediate (I) and small (B) LDL size subclasses were determined in 198 cases with asymptomatic carotid artery atherosclerosis (determined by B-mode ultrasonography) and 318 controls from the Atherosclerosis Risk in Communities (ARIC) Study. In Caucasians, a smaller LDL size was more prevalent in men and associated with a higher body mass index, hypertension prevalence, and plasma total- and LDL-cholesterol and triglycerides, but lower HDL-cholesterol. In African-Americans, a smaller LDL size was associated with higher triglycerides and lower HDL-cholesterol and hypertension prevalence. In Caucasians, Subclass B prevalence was 29.1% among cases and 14.8% among controls. The odds ratio (95% confidence interval) for Subclass B rather than Subclass A in Caucasian cases was 2.94 (1.67–5.17); the association remained significant after controlling for age, body mass index, smoking, and either plasma triglycerides or HDL-cholesterol. In African-Americans, however, there was no significant association between LDL subclass and case status. A predominance of smaller LDL particles is associated with asymptomatic carotid artery atherosclerosis in Caucasians, through mechanisms that remain to be elucidated. 相似文献