Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation
Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins trigg...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/950 |
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| author | Amelia Drysdale Maria Blanco-Lopez Stephen J. White Amanda J. Unsworth Sarah Jones |
| author_facet | Amelia Drysdale Maria Blanco-Lopez Stephen J. White Amanda J. Unsworth Sarah Jones |
| author_sort | Amelia Drysdale |
| collection | DOAJ |
| description | Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (<i>p</i> < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (<i>p</i> < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis. |
| first_indexed | 2024-03-08T09:53:35Z |
| format | Article |
| id | doaj.art-254e5f7d70ea48369f7e3d3b862fece9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:35Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-254e5f7d70ea48369f7e3d3b862fece92024-01-29T13:55:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125295010.3390/ijms25020950Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and ActivationAmelia Drysdale0Maria Blanco-Lopez1Stephen J. White2Amanda J. Unsworth3Sarah Jones4Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UKDepartment of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UKFaculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UKDepartment of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UKDepartment of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UKProteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (<i>p</i> < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (<i>p</i> < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis.https://www.mdpi.com/1422-0067/25/2/950atherosclerosisplaque ruptureplaque erosionplateletthrombosisextracellular matrix |
| spellingShingle | Amelia Drysdale Maria Blanco-Lopez Stephen J. White Amanda J. Unsworth Sarah Jones Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation International Journal of Molecular Sciences atherosclerosis plaque rupture plaque erosion platelet thrombosis extracellular matrix |
| title | Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation |
| title_full | Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation |
| title_fullStr | Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation |
| title_full_unstemmed | Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation |
| title_short | Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation |
| title_sort | differential proteoglycan expression in atherosclerosis alters platelet adhesion and activation |
| topic | atherosclerosis plaque rupture plaque erosion platelet thrombosis extracellular matrix |
| url | https://www.mdpi.com/1422-0067/25/2/950 |
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