Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype
Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more sta...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Stroke Society
2021-09-01
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| Series: | Journal of Stroke |
| Subjects: | |
| Online Access: | http://www.j-stroke.org/upload/pdf/jos-2021-00178.pdf |
| _version_ | 1818689548127830016 |
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| author | Annelie Shami Andreas Edsfeldt Eva Bengtsson Jan Nilsson Angela C. Shore Andrea Natali Faisel Khan Esther Lutgens Isabel Gonçalves |
| author_facet | Annelie Shami Andreas Edsfeldt Eva Bengtsson Jan Nilsson Angela C. Shore Andrea Natali Faisel Khan Esther Lutgens Isabel Gonçalves |
| author_sort | Annelie Shami |
| collection | DOAJ |
| description | Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD. |
| first_indexed | 2024-12-17T12:11:51Z |
| format | Article |
| id | doaj.art-a59fad5770eb4319b4cb7cdafcbcb201 |
| institution | Directory Open Access Journal |
| issn | 2287-6391 2287-6405 |
| language | English |
| last_indexed | 2024-12-17T12:11:51Z |
| publishDate | 2021-09-01 |
| publisher | Korean Stroke Society |
| record_format | Article |
| series | Journal of Stroke |
| spelling | doaj.art-a59fad5770eb4319b4cb7cdafcbcb2012022-12-21T21:49:23ZengKorean Stroke SocietyJournal of Stroke2287-63912287-64052021-09-0123336737610.5853/jos.2021.00178393Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable PhenotypeAnnelie Shami0Andreas Edsfeldt1Eva Bengtsson2Jan Nilsson3Angela C. Shore4Andrea Natali5Faisel Khan6Esther Lutgens7Isabel Gonçalves8 Department of Clinical Sciences Malmo, Clinical Research Center, Lund University, Malmo, Sweden Department of Clinical Sciences Malmo, Clinical Research Center, Lund University, Malmo, Sweden Department of Clinical Sciences Malmo, Clinical Research Center, Lund University, Malmo, Sweden Department of Clinical Sciences Malmo, Clinical Research Center, Lund University, Malmo, Sweden Diabetes and Vascular Medicine, University of Exeter Medical School, National Institute for Health Research Exeter Clinical Research Facility, Exeter, UK Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands Department of Clinical Sciences Malmo, Clinical Research Center, Lund University, Malmo, SwedenBackground and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.http://www.j-stroke.org/upload/pdf/jos-2021-00178.pdfcd40cd40 ligandatherosclerosiscarotid arteriesinflammation |
| spellingShingle | Annelie Shami Andreas Edsfeldt Eva Bengtsson Jan Nilsson Angela C. Shore Andrea Natali Faisel Khan Esther Lutgens Isabel Gonçalves Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype Journal of Stroke cd40 cd40 ligand atherosclerosis carotid arteries inflammation |
| title | Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype |
| title_full | Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype |
| title_fullStr | Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype |
| title_full_unstemmed | Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype |
| title_short | Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype |
| title_sort | soluble cd40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable phenotype |
| topic | cd40 cd40 ligand atherosclerosis carotid arteries inflammation |
| url | http://www.j-stroke.org/upload/pdf/jos-2021-00178.pdf |
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