Atherogenesis and plaque rupture, surface/interface-related phenomena
In atherogenesis, free oxygen radicals cause a lipid peroxidation of apoB100-containing lipoproteins in the blood, at the blood–endothelium-interface and in the subendothelial space. These lipoproteins easily aggregate, bind to their receptor heparan sulfate proteoglycan and calcify to arteriosclero...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/138392 |
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| author | Siegel, G. Berkholz, J. Klüßendorf, D. Knosalla, C. Zakrzewicz, A. Ermilov, E. Malmsten, M. Lindman, Bjorn |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Siegel, G. Berkholz, J. Klüßendorf, D. Knosalla, C. Zakrzewicz, A. Ermilov, E. Malmsten, M. Lindman, Bjorn |
| author_sort | Siegel, G. |
| collection | NTU |
| description | In atherogenesis, free oxygen radicals cause a lipid peroxidation of apoB100-containing lipoproteins in the blood, at the blood–endothelium-interface and in the subendothelial space. These lipoproteins easily aggregate, bind to their receptor heparan sulfate proteoglycan and calcify to arteriosclerotic nanoplaques (ternary complexes). Nanoplaque formation was measured by ellipsometry, both in vitro on an HS-PG coated hydrophobic silica surface and also in vivo on living human coronary endothelial cells, which had overgrown the silica surface. Reversely, we show with the same techniques that, in dependence on the degree of peroxidation and epitope in concern, oxLDL attacks its molecular receptor and thus can induce degradation of arteriosclerotic plaques and, in a combined action with inflammatory processes, even a plaque rupture. In a previous work, we had found PML-NB, fibrous cap (collagens, proteoglycans) and HSBGF binding sites (e.g., TGFβ1) up-regulated and NFκB down-regulated. With this background knowledge we created a molecular feedback control circuit model where PML-NB functions as regulation centre, fibrous cap as controlled variable, HSBGF binding sites as receptor and NFκB as effector. Since NFκB is inhibited by one reaction strand in this model and inhibits itself collagen and proteoglycan synthesis in the fibrous cap of the plaque, this double check (disinhibition) causes a stabilization of the fibrous cap through a specially strong collagen and proteoglycan production, which in addition is supported by circulating TGFβ. TGFβ furthers also calcification, so that fibrous cap tensile strength and resistance to shear stress are imparted. This way, a plaque rupture may possibly be averted. |
| first_indexed | 2025-02-19T03:56:14Z |
| format | Journal Article |
| id | ntu-10356/138392 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:56:14Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1383922020-06-01T10:01:34Z Atherogenesis and plaque rupture, surface/interface-related phenomena Siegel, G. Berkholz, J. Klüßendorf, D. Knosalla, C. Zakrzewicz, A. Ermilov, E. Malmsten, M. Lindman, Bjorn School of Materials Science & Engineering Engineering::Materials Atherogenesis And Plaque Rupture Oxidized Low-density Lipoprotein In atherogenesis, free oxygen radicals cause a lipid peroxidation of apoB100-containing lipoproteins in the blood, at the blood–endothelium-interface and in the subendothelial space. These lipoproteins easily aggregate, bind to their receptor heparan sulfate proteoglycan and calcify to arteriosclerotic nanoplaques (ternary complexes). Nanoplaque formation was measured by ellipsometry, both in vitro on an HS-PG coated hydrophobic silica surface and also in vivo on living human coronary endothelial cells, which had overgrown the silica surface. Reversely, we show with the same techniques that, in dependence on the degree of peroxidation and epitope in concern, oxLDL attacks its molecular receptor and thus can induce degradation of arteriosclerotic plaques and, in a combined action with inflammatory processes, even a plaque rupture. In a previous work, we had found PML-NB, fibrous cap (collagens, proteoglycans) and HSBGF binding sites (e.g., TGFβ1) up-regulated and NFκB down-regulated. With this background knowledge we created a molecular feedback control circuit model where PML-NB functions as regulation centre, fibrous cap as controlled variable, HSBGF binding sites as receptor and NFκB as effector. Since NFκB is inhibited by one reaction strand in this model and inhibits itself collagen and proteoglycan synthesis in the fibrous cap of the plaque, this double check (disinhibition) causes a stabilization of the fibrous cap through a specially strong collagen and proteoglycan production, which in addition is supported by circulating TGFβ. TGFβ furthers also calcification, so that fibrous cap tensile strength and resistance to shear stress are imparted. This way, a plaque rupture may possibly be averted. 2020-05-05T08:33:37Z 2020-05-05T08:33:37Z 2018 Journal Article Siegel, G., Berkholz, J., Klüßendorf, D., Knosalla, C., Zakrzewicz, A., Ermilov, E., . . . Lindman, B. (2018). Atherogenesis and plaque rupture, surface/interface-related phenomena. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 557, 28-35. doi:10.1016/j.colsurfa.2018.05.080 0927-7757 https://hdl.handle.net/10356/138392 10.1016/j.colsurfa.2018.05.080 2-s2.0-85048348580 557 28 35 en Colloids and Surfaces A: Physicochemical and Engineering Aspects © 2018 Elsevier B.V. All rights reserved. This paper was published in Colloids and Surfaces A: Physicochemical and Engineering Aspects and is made available with permission of Elsevier B.V. |
| spellingShingle | Engineering::Materials Atherogenesis And Plaque Rupture Oxidized Low-density Lipoprotein Siegel, G. Berkholz, J. Klüßendorf, D. Knosalla, C. Zakrzewicz, A. Ermilov, E. Malmsten, M. Lindman, Bjorn Atherogenesis and plaque rupture, surface/interface-related phenomena |
| title | Atherogenesis and plaque rupture, surface/interface-related phenomena |
| title_full | Atherogenesis and plaque rupture, surface/interface-related phenomena |
| title_fullStr | Atherogenesis and plaque rupture, surface/interface-related phenomena |
| title_full_unstemmed | Atherogenesis and plaque rupture, surface/interface-related phenomena |
| title_short | Atherogenesis and plaque rupture, surface/interface-related phenomena |
| title_sort | atherogenesis and plaque rupture surface interface related phenomena |
| topic | Engineering::Materials Atherogenesis And Plaque Rupture Oxidized Low-density Lipoprotein |
| url | https://hdl.handle.net/10356/138392 |
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