| 1. |
- Malmsten, M, et al.
(författare)
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A model substrate for ellipsometry studies of lipoprotein deposition at the endothelium
- 2001
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Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 240, s. 372-374
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cell layers from umbilical cords were grown on methylated silica surfaces. Fluorescence microscopy showed this layer to be confluent and to consist of living cells. Initial ellipsometry measurements were performed to illustrate both the stability of the model surface in ellipsometry measurements and the Ca2+-dependent binding of lipoproteins at the cell-based substrate. The present substrate holds promise as a model substrate for in vitro investigations of lipoprotein deposition at the endothelium surface under close to in vivo conditions.
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| 2. |
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| 3. |
- Malmsten, M, et al.
(författare)
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Ellipsometry studies of lipoprotein adsorption
- 2000
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Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 224, s. 338-346
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of a number of lipoproteins, i.e., low-density lipoprotein (LDL), oxidized LDL (oxLDL), high-density lipoprotein (HDL), and lipoprotein (a), at silica and methylated silica as well as at the latter surface modified through adsorption of proteoheparan sulfate, was investigated with in situ ellipsometry at close to physiological conditions. It was found that LDL, oxLDL, HDL, and lipoprotein (a) all adsorbed more extensively at silica than at methylated silica. Upon exposure of the methylated silica surface to proteoheparan sulfate, this proteoglycan adsorbs through its hydrophobic moiety, thereby forming a layer similar to that in the biological system, with the polysaccharide chains forming brushes oriented toward the aqueous solution. Analogous to the biological system, both lipoprotein (a) and LDL were found to deposit at such surfaces, the latter particularly in the simultaneous presence of Ca2+. After HDL pre-exposure, however, no LDL deposition was observed, even at high LDL and Ca2+ concentrations. These findings correlate well with those obtained from clinical investigations on risk factors for atherosclerosis.
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| 4. |
- Siegel, G, et al.
(författare)
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A primary lesion model for arteriosclerotic microplaque formation
- 2000
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Ingår i: International Journal of Angiology. - 1061-1711 .- 1615-5939. ; 9, s. 129-134
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Tidskriftsartikel (refereegranskat)abstract
- Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that HDL has a high binding affinity to the receptor and a protective effect on interfacial heparan sulfate proteoglycan layers with respect to LDL and Ca2+ complexation. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca2+ thus creating the ternary complex formation `proteoglycan-LDL-calcium'. This heterotrimeric complex build-up may be interpreted as arteriosclerotic microplaque formation on the molecular level responsible for the primary lesion. On the other hand, HDL bound to heparan sulfate proteoglycan protected against LDL docking and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL and garlic extract were able to reduce the ternary complex deposition.
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| 5. |
- Siegel, G, et al.
(författare)
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A receptor-based biosensor for lipoprotein docking at the endothelial surface and vascular matrix
- 2001
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Ingår i: Biosensors & bioelectronics. - 0956-5663 .- 1873-4235. ; 16, s. 895-904
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Tidskriftsartikel (refereegranskat)abstract
- Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that HDL has a high binding affinity to the receptor and a protective effect on interfacial heparan sulfate proteoglycan layers, with respect to LDL and Ca2+ complexation. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca2+, thus creating the complex formation `proteoglycan¯low density lipoprotein¯calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulfate proteoglycan protected against LDL docking and completely suppressed calcification of the proteoglycan¯lipoprotein complex. In addition, HDL and aqueous garlic extract were able to reduce the ternary complex deposition and to disintegrate HS-PG/LDL/Ca2+ aggregates. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a `nanoscopic' level under close to physiological conditions. In particular, Ca2+-promoted LDL deposition and the protective effect of HDL, even at high Ca2+ and LDL concentrations, agree well with previous clinical observations regarding risk and beneficial factors for early stages of atherosclerosis. Therefore, we believe that the system can be of some use in investigations, e.g. of the interplay between different lipoproteins in arteriosclerotic plaque formation, as well as in high throughput screening of candidate drugs to atherosclerosis in a biosensor application
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