VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling
Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality and morbidity worldwide. Lipid-lowering drugs, such as statins and proprotein convertase subtilisin/kexin type 9 inhibitors, are effective in reducing plasma low-density lipoprotein cholesterol levels and the ri...
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Elsevier
2025-08-01
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| author | Suha Jarad Govind Gill Peter Amadi Hong-mei Gu Da-wei Zhang |
| author_facet | Suha Jarad Govind Gill Peter Amadi Hong-mei Gu Da-wei Zhang |
| author_sort | Suha Jarad |
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| description | Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality and morbidity worldwide. Lipid-lowering drugs, such as statins and proprotein convertase subtilisin/kexin type 9 inhibitors, are effective in reducing plasma low-density lipoprotein cholesterol levels and the risk of ASCVD. However, the residual risk of ASCVD remains very high. Therefore, new strategies to treat ASCVD are urgently needed. Vascular smooth muscle cells (VSMCs) are essential contributors to atherosclerosis development and progression, with more than 50 % of atherosclerotic foam cells originating from VSMCs. VSMCs are characterized by their plasticity and ability to switch phenotype in response to the changing environment of atherosclerotic lesions, starting from the early stage of intimal thickening to the most advanced atherosclerotic lesions. However, VSMCs do not act independently, they interact with neighbouring cells and respond to the surrounding growth factors and cytokines by modulating their protein expression and changing their phenotype. Therefore, the main functions of VSMCs in atherosclerosis will be influenced, including the production of extracellular matrix (ECM) proteins and the maintenance of atherosclerotic plaque stability. In this review, we summarize the current understanding of VSMCs in atherosclerosis, focusing on their origin, plasticity, phenotype switching, and role at different stages of atherosclerosis. Furthermore, we highlight the influence of growth factors and cytokines on VSMC behaviour in atherosclerosis and discuss the role of ECM remodelling, specifically by integrins and matrix metalloproteinases, on VSMCs in atherosclerosis. Finally, we focus on current therapeutic strategies and options to target VSMCs in atherosclerosis management. |
| format | Article |
| id | doaj-art-f331f6be71c14cd39628d1f8babe5fed |
| institution | DOAJ |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| spelling | doaj-art-f331f6be71c14cd39628d1f8babe5fed2025-08-20T02:45:42ZengElsevierPharmacological Research1096-11862025-08-0121810783310.1016/j.phrs.2025.107833VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodellingSuha Jarad0Govind Gill1Peter Amadi2Hong-mei Gu3Da-wei Zhang4The Department of Biochemistry and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, CanadaThe Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, CanadaThe Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, CanadaThe Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, CanadaThe Department of Biochemistry and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; The Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Correspondence to: Department of Pediatrics, Group on the Molecular and Cell Biology of Lipids, University of Alberta, 303 Heritage Medical Research Centre, Edmonton, AB T6R 2G3, Canada.Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality and morbidity worldwide. Lipid-lowering drugs, such as statins and proprotein convertase subtilisin/kexin type 9 inhibitors, are effective in reducing plasma low-density lipoprotein cholesterol levels and the risk of ASCVD. However, the residual risk of ASCVD remains very high. Therefore, new strategies to treat ASCVD are urgently needed. Vascular smooth muscle cells (VSMCs) are essential contributors to atherosclerosis development and progression, with more than 50 % of atherosclerotic foam cells originating from VSMCs. VSMCs are characterized by their plasticity and ability to switch phenotype in response to the changing environment of atherosclerotic lesions, starting from the early stage of intimal thickening to the most advanced atherosclerotic lesions. However, VSMCs do not act independently, they interact with neighbouring cells and respond to the surrounding growth factors and cytokines by modulating their protein expression and changing their phenotype. Therefore, the main functions of VSMCs in atherosclerosis will be influenced, including the production of extracellular matrix (ECM) proteins and the maintenance of atherosclerotic plaque stability. In this review, we summarize the current understanding of VSMCs in atherosclerosis, focusing on their origin, plasticity, phenotype switching, and role at different stages of atherosclerosis. Furthermore, we highlight the influence of growth factors and cytokines on VSMC behaviour in atherosclerosis and discuss the role of ECM remodelling, specifically by integrins and matrix metalloproteinases, on VSMCs in atherosclerosis. Finally, we focus on current therapeutic strategies and options to target VSMCs in atherosclerosis management.http://www.sciencedirect.com/science/article/pii/S1043661825002580Macrophagessmooth muscle cellscardiovascular diseaseinflammationmatrix metalloproteinasecell migration |
| spellingShingle | Suha Jarad Govind Gill Peter Amadi Hong-mei Gu Da-wei Zhang VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling Pharmacological Research Macrophages smooth muscle cells cardiovascular disease inflammation matrix metalloproteinase cell migration |
| title | VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling |
| title_full | VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling |
| title_fullStr | VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling |
| title_full_unstemmed | VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling |
| title_short | VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling |
| title_sort | vsmcs in atherosclerosis implications on the role of inflammation and extracellular matrix remodelling |
| topic | Macrophages smooth muscle cells cardiovascular disease inflammation matrix metalloproteinase cell migration |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825002580 |
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