Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate
Atherosclerosis is one of the leading causes of mortality and morbidity worldwide. Chemokines and their receptors are implicated in the pathogenesis of atherosclerosis. CXCL12 is a member of the chemokine family exerting a myriad role in atherosclerosis through its classical CXCR4 and atypical ACKR3...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | Annals of Medicine |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2021.1974084 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849340296944418816 |
|---|---|
| author | Hussam A. S. Murad Misbahuddin M. Rafeeq Thamer M. A. Alqurashi |
| author_facet | Hussam A. S. Murad Misbahuddin M. Rafeeq Thamer M. A. Alqurashi |
| author_sort | Hussam A. S. Murad |
| collection | DOAJ |
| description | Atherosclerosis is one of the leading causes of mortality and morbidity worldwide. Chemokines and their receptors are implicated in the pathogenesis of atherosclerosis. CXCL12 is a member of the chemokine family exerting a myriad role in atherosclerosis through its classical CXCR4 and atypical ACKR3 (CXCR7) receptors. The modulatory and regulatory functional spectrum of CXCL12/CXCR4/ACKR3 axis in atherosclerosis spans from proatherogenic, prothrombotic and proinflammatory to atheroprotective, plaque stabilizer and dyslipidemia rectifier. This diverse continuum is executed in a wide range of biological units including endothelial cells (ECs), progenitor cells, macrophages, monocytes, platelets, lymphocytes, neutrophils and vascular smooth muscle cells (VSMCs) through complex heterogeneous and homogenous coupling of CXCR4 and ACKR3 receptors, employing different downstream signalling pathways, which often cross-talk among themselves and with other signalling interactomes. Hence, a better understanding of this structural and functional heterogeneity and complex phenomenon involving CXCL12/CXCR4/ACKR3 axis in atherosclerosis would not only help in formulation of novel therapeutics, but also in elucidation of the CXCL12 ligand and its receptors, as possible diagnostic and prognostic biomarkers.Key messagesThe role of CXCL12 per se is proatherogenic in atherosclerosis development and progression.The CXCL12 receptors, CXCR4 and ACKR3 perform both proatherogenic and athero-protective functions in various cell typesDue to functional heterogeneity and cross talk of CXCR4 and ACKR3 at receptor level and downstream pathways, regional boosting with specific temporal and spatial modulators of CXCL12, CXCR4 and ACKR3 need to be explored. |
| format | Article |
| id | doaj-art-1a428290503143c4907b4deaa4fd2f6f |
| institution | Kabale University |
| issn | 0785-3890 1365-2060 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj-art-1a428290503143c4907b4deaa4fd2f6f2025-08-20T03:43:57ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602021-01-015311598161210.1080/07853890.2021.1974084Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debateHussam A. S. Murad0Misbahuddin M. Rafeeq1Thamer M. A. Alqurashi2Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University (KAU), Jeddah, Saudi ArabiaDepartment of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University (KAU), Jeddah, Saudi ArabiaDepartment of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University (KAU), Jeddah, Saudi ArabiaAtherosclerosis is one of the leading causes of mortality and morbidity worldwide. Chemokines and their receptors are implicated in the pathogenesis of atherosclerosis. CXCL12 is a member of the chemokine family exerting a myriad role in atherosclerosis through its classical CXCR4 and atypical ACKR3 (CXCR7) receptors. The modulatory and regulatory functional spectrum of CXCL12/CXCR4/ACKR3 axis in atherosclerosis spans from proatherogenic, prothrombotic and proinflammatory to atheroprotective, plaque stabilizer and dyslipidemia rectifier. This diverse continuum is executed in a wide range of biological units including endothelial cells (ECs), progenitor cells, macrophages, monocytes, platelets, lymphocytes, neutrophils and vascular smooth muscle cells (VSMCs) through complex heterogeneous and homogenous coupling of CXCR4 and ACKR3 receptors, employing different downstream signalling pathways, which often cross-talk among themselves and with other signalling interactomes. Hence, a better understanding of this structural and functional heterogeneity and complex phenomenon involving CXCL12/CXCR4/ACKR3 axis in atherosclerosis would not only help in formulation of novel therapeutics, but also in elucidation of the CXCL12 ligand and its receptors, as possible diagnostic and prognostic biomarkers.Key messagesThe role of CXCL12 per se is proatherogenic in atherosclerosis development and progression.The CXCL12 receptors, CXCR4 and ACKR3 perform both proatherogenic and athero-protective functions in various cell typesDue to functional heterogeneity and cross talk of CXCR4 and ACKR3 at receptor level and downstream pathways, regional boosting with specific temporal and spatial modulators of CXCL12, CXCR4 and ACKR3 need to be explored.https://www.tandfonline.com/doi/10.1080/07853890.2021.1974084Cardiovasculardyslipidaemiainflammationinjurythrombosis |
| spellingShingle | Hussam A. S. Murad Misbahuddin M. Rafeeq Thamer M. A. Alqurashi Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate Annals of Medicine Cardiovascular dyslipidaemia inflammation injury thrombosis |
| title | Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate |
| title_full | Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate |
| title_fullStr | Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate |
| title_full_unstemmed | Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate |
| title_short | Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate |
| title_sort | role and implications of the cxcl12 cxcr4 cxcr7 axis in atherosclerosis still a debate |
| topic | Cardiovascular dyslipidaemia inflammation injury thrombosis |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2021.1974084 |
| work_keys_str_mv | AT hussamasmurad roleandimplicationsofthecxcl12cxcr4cxcr7axisinatherosclerosisstilladebate AT misbahuddinmrafeeq roleandimplicationsofthecxcl12cxcr4cxcr7axisinatherosclerosisstilladebate AT thamermaalqurashi roleandimplicationsofthecxcl12cxcr4cxcr7axisinatherosclerosisstilladebate |