Comparison of apoprotein B of low density lipoproteins of human interstitial fluid and plasma.
Ontology highlight
ABSTRACT:
SUBMITTER: Hong JL
PROVIDER: S-EPMC1144142 | biostudies-other | 1984 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Very low-density lipoprotein (VLDL) is the main plasma carrier of triacylglycerol that is elevated in pathological conditions such as diabetes, metabolic syndrome, obesity and dyslipidemia. How variations in triacylglycerol levels influence structural stability and remodeling of VLDL and its metabolic product, low-density lipoproteins (LDL), is unknown. We applied a biochemical and biophysical approach using lipoprotein remodeling by lipoprotein lipase and cholesterol ester transfer protein, along with thermal denaturation that mimics key aspects of lipoprotein remodeling in vivo. The results revealed that increasing the triacylglycerol content in VLDL promotes changes in the lipoprotein size and release of the exchangeable apolipoproteins. Similarly, increased triacylglycerol content in LDL promotes lipoprotein remodeling and fusion. These effects were observed in single-donor lipoproteins from healthy subjects enriched in exogenous triolein, in single-donor lipoproteins from healthy subjects with naturally occurring differences in endogenous triacylglycerol, and in LDL and VLDL from pooled plasma of diabetic and normolipidemic patients. Consequently, triacylglycerol-induced destabilization is a general property of plasma lipoproteins. This destabilization reflects a direct effect of triacylglycerol on lipoproteins. Moreover, we show that TG can act indirectly by increasing lipoprotein susceptibility to oxidation and lipolysis and thereby promoting the generation of free fatty acids that augment fusion. These in vitro findings are relevant to lipoprotein remodeling and fusion in vivo. In fact, fusion of LDL and VLDL enhances their retention in the arterial wall and, according to the response-to-retention hypothesis, triggers atherosclerosis. Therefore, enhanced fusion of triacylglycerol-rich lipoproteins suggests a new causative link between elevated plasma triacylglycerol and atherosclerosis.
| S-EPMC6482102 | biostudies-literature
Project description:BackgroundTraditionally, the impact of lipoproteins on vascular disease has been evaluated in light of their quantity, that is, cholesterol content, in plasma. However, recent studies of high-density lipoproteins (HDLs) have focused on functionality with regard to atheroprotection. For example, bioassays have emerged to assess the ability of HDL, in its near native plasma environment, to promote cholesterol removal (efflux) from cells. As a result, attention has focused on developing plasma-based assays for other putative HDL protective functions including protecting low-density lipoproteins (LDLs) from oxidative damage.ObjectiveTo determine the feasibility of such an assay in a complex sample such as plasma, we evaluated the contribution of HDL vs other plasma factors in preventing LDL oxidation.MethodsWe separated normolipidemic human plasma by gel filtration chromatography and assessed each fraction for its ability to prevent LDL modification by water soluble radical and copper-initiated oxidation mechanisms.ResultsUsing proteomics and selective precipitation methods, we identified major antioxidative contributions for fibrinogen, immunoglobulin G, albumin, and small soluble molecules like uric acid and ascorbate, with albumin being especially dominant in copper-initiated mechanisms. HDL particles were minor contributors (∼1%-2%) to the antioxidant capacity of plasma, irrespective of oxidation mechanism.ConclusionsGiven the overwhelming background of antioxidant capacity inherent to highly abundant plasma proteins, specific bioassays of HDL antioxidative function will likely require its complete separation from plasma.
| S-EPMC6437770 | biostudies-literature
Project description:Very low-density lipoproteins (VLDL) are precursors of low-density lipoproteins (LDL, or "bad cholesterol"). Factors affecting structural integrity of VLDL are important for their metabolism. To assess the role of electrostatic interactions in VLDL stability, we determined how solvent ionic conditions affect the heat-induced VLDL remodeling. This remodeling involves VLDL fusion, rupture, and fission of apolipoprotein E-containing high-density lipoprotein-(HDL-) like particles similar to those formed during VLDL-to-LDL maturation. Circular dichroism and turbidity show that increasing sodium salt concentration in millimolar range reduces VLDL stability and its enthalpic component. Consequently, favorable electrostatic interactions stabilize VLDL. Reduction in pH from 7.4 to 6.0 reduces VLDL stability, with further destabilization detected at pH < 6, which probably results from titration of the N-terminal ?-amino groups and free fatty acids. This destabilization is expected to facilitate endosomal degradation of VLDL, promote their coalescence into lipid droplets in atherosclerotic plaques, and affect their potential use as drug carriers.
| S-EPMC3136112 | biostudies-literature
Project description:Human VLDLs assembled in the liver and secreted into the circulation supply energy to peripheral tissues. VLDL lipolysis yields atherogenic LDLs and VLDL remnants that strongly correlate with CVD. Although the composition of VLDL particles has been well-characterized, their 3D structure is elusive because of their variations in size, heterogeneity in composition, structural flexibility, and mobility in solution. Here, we employed cryo-electron microscopy and individual-particle electron tomography to study the 3D structure of individual VLDL particles (without averaging) at both below and above their lipid phase transition temperatures. The 3D reconstructions of VLDL and VLDL bound to antibodies revealed an unexpected polyhedral shape, in contrast to the generally accepted model of a spherical emulsion-like particle. The smaller curvature of surface lipids compared with HDL may also reduce surface hydrophobicity, resulting in lower binding affinity to the hydrophobic distal end of the N-terminal ?-barrel domain of cholesteryl ester transfer protein (CETP) compared with HDL. The directional binding of CETP to HDL and VLDL may explain the function of CETP in transferring TGs and cholesteryl esters between these particles. This first visualization of the 3D structure of VLDL could improve our understanding of the role of VLDL in atherogenesis.
| S-EPMC5036368 | biostudies-literature
Project description:BackgroundRecent technical advances in the extraction of dermal interstitial fluid (ISF) have stimulated interest in using this rather unexploited biofluid as an alternative to blood for detection and prediction of disease. However, knowledge about the presence of useful biomarkers for health monitoring in ISF is still limited. In this study, we characterized the lipidome of human suction blister fluid (SBF) as a surrogate for pure ISF and compared it to that of plasma.MethodsPlasma and SBF samples were obtained from 18 healthy human volunteers after an overnight fast. Total lipids were extracted and analyzed by liquid chromatography-tandem mass spectrometry. One hundred ninety-three lipid species covering 10 complex lipid classes were detected and quantified in both plasma and SBF using multiple reaction monitoring. A fraction of the lipid extract was subjected to alkaline transesterification and fatty acid methyl esters were analyzed by gas chromatography-mass spectrometry.ResultsThe total concentration of lipids in SBF was 17% of the plasma lipid concentration. The molar fraction of lipid species within lipid classes, as well as total fatty acids, showed a generally high correlation between plasma and SBF. However, SBF had larger fractions of lysophospholipids and diglycerides relative to plasma, and consequently less diacylphospholipids and triglycerides. Principal component analysis revealed that the interindividual variation in SBF lipid profiles was considerably larger than the within-subject variation between plasma and SBF.ConclusionsPlasma and SBF lipid profiles show high correlation and SBF could be used interchangeably with blood for the analysis of major lipids used in health monitoring.
| S-EPMC6708155 | biostudies-literature
Project description:The study aimed to assess the strength of the relationships between small dense low-density lipoproteins (sdLDL) and other parameters describing metabolic disorders and determine which of the lipid profile parameters can be used as markers of increased sdLDL concentration. The proposed model of sdLDL (examined by heparin-magnesium precipitation method) as a function of lipid parameters and atherogenic plasma indexes non-high-dense lipoproteins (non-HDL) and total cholesterol to high-dense lipoprotein ratio (TC/HDL), Atherogenic plasma index (API) is based on data from 485 participants divided into two age groups, <35≥ years. In multiple linear regression, sdLDL concentration was associated with the concentration of non-HDL-C (p = 0.043) and API value (p < 0.001) in participants <35 years, and with non-HDL-C (p < 0.001) and triglycerides (p = 0.020) concentration ≥35 years. The presence of abnormal values of API in participants <35 years and non-HDL-C in participants ≥35 years is a significant factor increasing the chances of the highest sdLDL (≥1.03 mmol/L) corresponding to Q4 in people without metabolic disorders. Different lipid parameters and atherogenicity indexes are associated with a high concentration of sdLDL depending on the age group. Abnormal API <35 years and non-HDL ≥35 years are associated with the highest sdLDL values and may be an indication for further specialist diagnosis of cardiovascular disease risk factors.
| S-EPMC9102874 | biostudies-literature
Project description:BackgroundOxidized low-density lipoprotein (oxLDL) uptake by macrophages plays an important role in foam cell formation. It has been suggested the presence of heterogeneous subsets of macrophage, such as M1 and M2, in human atherosclerotic lesions. To evaluate which types of macrophages contribute to atherogenesis, we performed cDNA microarray analysis to determine oxLDL-induced transcriptional alterations of each subset of macrophages.ResultsHuman monocyte-derived macrophages were polarized toward the M1 or M2 subset, followed by treatment with oxLDL. Then gene expression levels during oxLDL treatment in each subset of macrophages were evaluated by cDNA microarray analysis and quantitative real-time RT-PCR. In terms of high-ranking upregulated genes and functional ontologies, the alterations during oxLDL treatment in M2 macrophages were similar to those in nonpolarized macrophages (M0). Molecular network analysis showed that most of the molecules in the oxLDL-induced highest scoring molecular network of M1 macrophages were directly or indirectly related to transforming growth factor (TGF)-β1. Hierarchical cluster analysis revealed commonly upregulated genes in all subset of macrophages, some of which contained antioxidant response elements (ARE) in their promoter regions. A cluster of genes that were specifically upregulated in M1 macrophages included those encoding molecules related to nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling pathway. Quantitative real-time RT-PCR showed that the gene expression of interleukin (IL)-8 after oxLDL treatment in M2 macrophages was markedly lower than those in M0 and M1 cells. HMOX1 gene expression levels were almost the same in all 3 subsets of macrophages even after oxLDL treatment.ConclusionsThe present study demonstrated transcriptional alterations in polarized macrophages during oxLDL treatment. The data suggested that oxLDL uptake may affect TGF-β1- and NF-κB-mediated functions of M1 macrophages, but not those of M0 or M2 macrophages. It is likely that M1 macrophages characteristically respond to oxLDL.
| S-EPMC3022593 | biostudies-literature
Project description:High-density lipoproteins (HDLs) mediate cholesterol transport and protection from cardiovascular disease. Although synthetic HDLs have been studied for 30 years, the structures of human plasma-derived HDL and its major protein apolipoprotein apoA-I are unknown. We separated normal human HDL into five density subfractions and then further isolated those containing predominantly apoA-I (LpA-I). Using cross-linking chemistry and mass spectrometry, we found that apoA-I adopts a structural framework in these particles that closely mirrors that in synthetic HDL. We adapted established structures for synthetic HDL to generate the first detailed models of authentic human plasma HDL in which apoA-I adopts a symmetrical cage-like structure. The models suggest that HDL particle size is modulated by means of a twisting motion of the resident apoA-I molecules. This understanding offers insights into how apoA-I structure modulates HDL function and its interactions with other apolipoproteins.
| S-EPMC3079355 | biostudies-literature
Project description:The purpose of this study is to compare the effect of the different physical factors on low-density lipoproteins (LDL) accumulation from flowing blood to the arterial wall of the left coronary arteries. The three-dimensional (3D) computational model of the left coronary arterial tree is reconstructed from a patient-specific computed tomography angiography (CTA) image. The endothelium of the coronary artery is represented by a shear stress dependent three-pore model. Fluid-structure interaction ([Formula: see text]) based numerical method is used to study the LDL transport from vascular lumen into the arterial wall. The results show that the high elastic property of the arterial wall decreases the complexity of the local flow field in the coronary bifurcation system. The places of high levels of LDL uptake coincide with the regions of low wall shear stress. In addition, hypertension promotes LDL uptake from flowing blood in the arterial wall, while the thickened arterial wall decreases this process. The present computer strategy combining the methods of coronary CTA image 3D reconstruction, [Formula: see text] simulation, and three-pore modeling was illustrated to be effective on the simulation of the distribution and the uptake of LDL. This may have great potential for the early prediction of the local atherosclerosis lesion in the human left coronary artery.
| S-EPMC7910311 | biostudies-literature
Project description:Intermediate-density lipoproteins (IDLs), the remnants of very-low-density lipoproteins via lipolysis, are rich in cholesteryl ester and are associated with cardiovascular disease. Despite pharmacological interest in IDLs, their three-dimensional (3D) structure is still undetermined due to their variation in size, composition, and dynamic structure. To explore the 3D structure of IDLs, we reconstructed 3D density maps from individual IDL particles using cryo-electron microscopy (cryo-EM) and individual-particle electron tomography (IPET, without averaging from different molecules). 3D reconstructions of IDLs revealed an unexpected polyhedral structure that deviates from the generally assumed spherical shape model (Frias et al., 2007; Olson, 1998; Shen et al., 1977). The polyhedral-shaped IDL contains a high-density shell formed by flat surfaces that are similar to those of very-low-density lipoproteins but have sharper dihedral angles between nearby surfaces. These flat surfaces would be less hydrophobic than the curved surface of mature spherical high-density lipoprotein (HDL), leading to a lower binding affinity of IDL to hydrophobic proteins (such as cholesteryl ester transfer protein) than HDL. This is the first visualization of the IDL 3D structure, which could provide fundamental clues for delineating the role of IDL in lipid metabolism and cardiovascular disease.
| S-EPMC6409128 | biostudies-literature