Abstract：
:Endothelial dysfunction is a key step in atherosclerosis development. Our recent studies suggested that oxLDL-induced increase in endothelial stiffness plays a major role in dyslipidemia-induced endothelial dysfunction. In this study, we identify oxysterols, as the major component of oxLDL, responsible for the increase in endothelial stiffness. Using Atomic Force Microscopy to measure endothelial elastic modulus, we show that endothelial stiffness increases with progressive oxidation of LDL and that the two lipid fractions that contribute to endothelial stiffening are oxysterols and oxidized phosphatidylcholines, with oxysterols having the dominant effect. Furthermore, endothelial elastic modulus increases as a linear function of oxysterol content of oxLDL. Specific oxysterols, however, have differential effects on endothelial stiffness with 7-ketocholesterol and 7α-hydroxycholesterol, the two major oxysterols in oxLDL, having the strongest effects. 27-hydroxycholesterol, found in atherosclerotic lesions, also induces endothelial stiffening. For all oxysterols, endothelial stiffening is reversible by enriching the cells with cholesterol. oxLDL-induced stiffening is accompanied by incorporation of oxysterols into endothelial cells. We find significant accumulation of three oxysterols, 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol, in mouse aortas of dyslipidemic ApoE⁻/⁻ mice at the early stage of atherosclerosis. Remarkably, these are the same oxysterols we have identified to induce endothelial stiffening.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Shentu TP,Singh DK,Oh MJ,Sun S,Sadaat L,Makino A,Mazzone T,Subbaiah PV,Cho M,Levitan Idoi
10.1194/jlr.M027102subject
Has Abstractpub_date
2012-07-01 00:00:00pages
1348-58issue
7eissn
0022-2275issn
1539-7262pii
jlr.M027102journal_volume
53pub_type
杂志文章abstract：:Four groups of 20 weanling swine each were fed either (a) basal diet, (b) basal plus hydrogenated fat (13% trans), (c) basal plus hydrogenated fat (13% trans) and 0.4% cholesterol, or (d) basal plus beef tallow (all cis). After six months of feeding, the animals were killed and the blood and aortas were removed. Very ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-03-01 00:00:00
abstract：:To consider possible interaction of the phospholipid membrane with calcium ions, crystal structures of calcium dl-alpha- and beta-glycerophosphates (alpha- and beta-CaGs, respectively) were investigated by X-ray diffraction methods. After many attempts, relatively large single crystals of beta-CaG were prepared from t...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has been applied primarily to the analysis of glycosphingolipids separated from other complex mixtures by TLC, but it is difficult to obtain quantitative profiling of each glycosphingolipid among the different spots on TLC by MALDI-MS. Thus, the ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D800038-JLR200
更新日期：2008-12-01 00:00:00
abstract：:The expansion of lipid droplets (LDs) and the differentiation of preadipocytes are two important aspects of mammalian lipid storage. In this study, we examined the role of CDP-diacylglycerol (DAG) synthases (CDSs), encoded by CDS1 and CDS2 genes in mammals, in lipid storage. CDS enzymes catalyze the formation of CDP-D...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M060574
更新日期：2016-05-01 00:00:00
abstract：:Mice with a targeted mutation of 3beta-hydroxysterol Delta(7)-reductase (Dhcr7) that cannot convert 7-dehydrocholesterol to cholesterol were used to identify the origin of fetal sterols. Because their heterozygous mothers synthesize cholesterol normally, virtually all sterols found in a Dhcr7 knockout fetus having a D...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600141-JLR200
更新日期：2006-07-01 00:00:00
abstract：:Thioesterase superfamily member 1 (Them1; synonyms acyl-CoA thioesterase 11 and StarD14) is highly expressed in brown adipose tissue and limits energy expenditure in mice. Them1 is a putative fatty acyl-CoA thioesterase that comprises tandem hot dog-fold thioesterase domains and a lipid-binding C-terminal steroidogeni...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M029538
更新日期：2012-12-01 00:00:00
abstract：:Hepatocytes express on their surfaces more than one class of receptors capable of mediating the internalization of lipoproteins. However, relatively little is known about the binding characteristics of hepatic receptors for various lipoproteins, about the regulation of the receptors, and about the consequences for int...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-12-01 00:00:00
abstract：:The addition of a trans isomer of arachidonic acid (20:4 delta 14trans) to rat platelet suspensions inhibited the aggregation induced by 7.5 microM of arachidonic acid. This inhibitory effect of 20:4 delta 14trans was significant at concentrations of 7.5-22.5 microM and the range of inhibition was 20% at an inhibitor/...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Distinct isoforms of long-chain acyl-CoA synthetases (ACSLs) may partition fatty acids toward specific metabolic cellular pathways. For each of the five members of the rat ACSL family, we analyzed tissue mRNA distributions, and we correlated the mRNA, protein, and activity of ACSL1 and ACSL4 after fasting and refeedin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600150-JLR200
更新日期：2006-09-01 00:00:00
abstract：:Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL's ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000767
更新日期：2020-11-03 00:00:00
abstract：:Fatty acid translocase (FAT/CD36) is a membrane protein putatively involved in the transmembrane transport of long-chain fatty acids. We tested the hypothesis that expression of this protein in H9c2, a rat heart cell line normally not expressing FAT, would increase cellular palmitate uptake. We were able to stably tra...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:Liver and kidney microsomes have been found to catalyze a rapid decarboxylation of retinoic acid in vitro. The reaction requires NADPH and Fe(2+), and is further stimulated by the presence of pyrophosphate. Thiamine pyrophosphate contained sufficient iron as an impurity to provide strong enhancement of the reaction in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-07-01 00:00:00
abstract：:Paraoxonases (PONs) are a small family of antioxidant enzymes whose antiatherogenic activity is well known. The aim of the present study was the evaluation of the effects of moderate aerobic training on their expression using a rat model. In order to discriminate between PON1 and PON3 enzymatic activity, we took advan...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800493-JLR200
更新日期：2009-10-01 00:00:00
abstract：:This paper presents a case of typical hyperlipoproteinemia type I in a young woman. Her serum triglycerides varied between 2 and 90 mmol/l and she had substantial amounts of apolipoprotein B-48 in fasting plasma. She had no detectable lipoprotein lipase (LPL) activity in post-heparin plasma (less than 0.2 percent of n...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:The metabolism of chenodeoxycholic acid by Pseudomonas sp. NCIB 10590 under strict anaerobic conditions was studied. A range of unsaturated acidic and neutral metabolites were isolated and identified. The major acidic product was chola-4,6-dien-3-one-24-oic acid whilst the major neutral product was androsta-4,6-dien-3...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive N-methyl-d-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain ar...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700406-JLR200
更新日期：2008-01-01 00:00:00
abstract：:The human retina is well-known to have unique lipid profiles enriched in long-chain polyunsaturated fatty acids (LC-PUFAs) and very long-chain polyunsaturated fatty acids (VLC-PUFAs) that appear to promote normal retinal structure and function, but the influence of diet on retinal lipid profiles in health and disease ...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P065540
更新日期：2016-03-01 00:00:00
abstract：:Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essent...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.TR119000383
更新日期：2020-05-01 00:00:00
abstract：:We analyzed Niemann-Pick type C disease 1 (NPC1) gene in 12 patients with Niemann-Pick type C disease by sequencing both cDNA obtained from fibroblasts and genomic DNA. All the patients were compound heterozygotes. We found 15 mutations, eight of which previously unreported. The comparison of cDNA and genomic DNA reve...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200203-jlr200
更新日期：2002-11-01 00:00:00
abstract：:Lipogenesis in vitro from acetate-1-(14)C was studied in human preputial skin and abdominal skin. Radioactive lipids were separated by column chromatography on Florisil and by thin-layer chromatography on silica gel. Radioactivity was incorporated chiefly into the triglyceride, sterol, and polar lipid fractions, while...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-09-01 00:00:00
abstract：:Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nucl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044032
更新日期：2014-05-01 00:00:00
abstract：:The apolipoprotein (apo) B-100-specific monoclonal antibody MB47 has been widely used in lipoprotein metabolism and atherosclerosis research. When bound to apoB-100 on low density lipoproteins (LDL), antibody MB47 completely blocks the binding of LDL to the LDL receptor. The epitope for antibody MB47 has previously be...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Phosphorylcholine-1,2-(14)C and choline-1,2-(14)C-labeled cytidine diphosphate choline are incorporated into lecithin by whole homogenates and particulate fractions of rat retina with optimal incorporation of label by the microsomal fraction. The soluble fraction contains a factor(s) which stimulates incorporation of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-11-01 00:00:00
abstract：:The ternary phase diagram of cholesteryl myristate--dimyristoyl lecithin--water has been determined by polarizing light microscopy, scanning calorimetry, and x-ray diffraction. Hydrated dimyristoyl lecithin forms a lamellar liquid--crystalline phase (L alpha) at temperatures greater than 23 degrees C into which limite...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:Fatty acid elongases and desaturases play an important role in hepatic and whole body lipid composition. We examined the role that key transcription factors played in the control of hepatic elongase and desaturase expression. Studies with peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice esta...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600177-JLR200
更新日期：2006-09-01 00:00:00
abstract：:Delta 6 desaturase (FADS2) is a critical bifunctional enzyme required for PUFA biosynthesis. In some organisms, FADS2s have high substrate specificity, whereas in others, they have high catalytic activity. Previously, we analyzed the molecular mechanisms underlying high FADS2 substrate specificity; in this study, we a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M079806
更新日期：2018-01-01 00:00:00
abstract：:To obtain a panel of monoclonal antibodies (MAbs) to study the folding and conformation of the low density lipoprotein receptor (LDLr), we have generated hybridomas from LDLr-deficient mice that had been immunized with the extracellular domain of the human LDLr. The 12 MAbs were specific for the ligand binding domain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600130-JLR200
更新日期：2006-07-01 00:00:00
abstract：:Very few studies have investigated the interrelations between proprotein convertase subtilisin/kexin type 9 (PCSK9) metabolism, cholesterol synthesis, and cholesterol absorption. We aimed to address this issue in a large clinical trial of 245 patients with hypercholesterolemia. Serum lipids, PCSK9, lathosterol (choles...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P088583
更新日期：2019-01-01 00:00:00
abstract：:A device that lowers a micropipet into position just above a thin-layer plate is described. Use of a self-filling pipet and foot-operated bellows allows one to apply many portions of a sample to the same point at high speed without damaging the adsorbent coating. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-11-01 00:00:00
abstract：:Feeding of phytol in large doses (2-5% by weight in the diet) led to accumulation of phytanic acid in the mouse, rat, rabbit, and chinchilla, the degree of accumulation depending upon the level of dietary intake. The relative concentration of phytanic acid, expressed as a percentage of the total fatty acids, was as hi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-09-01 00:00:00
