ArticleCardiovascular research2023
Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Tissue-Specific Chemerin in Atherosclerosis.Biomolecules · 2026Review
- Macrophage CCRL2 promotes NLRP3 inflammasome activation to exacerbate atherosclerosis.Cellular & molecular immunology · 2026Article
- Endothelial cells modulate immune cell responses during atherosclerosis.Trends in immunology · 2026Review
- Decoding chemerin proteolytic processing and isoform signaling across disease contexts.iScience · 2026Review
- ChemR23 prevents phenotypic switching of vascular smooth muscle cells into macrophage-like foam cells in atherosclerosis.Cardiovascular research · 2026Article
- Silent Myocardial Infarction Revisited: Immuno-metabolic Mechanisms, Multimodal Biomarkers, and Translational Diagnostics.Journal of cardiovascular translational research · 2026Review
- Chemerin/ChemerinR1 axis and inflammation-related diseases.Frontiers in molecular biosciences · 2026Review
- Multiscale Computational Dissection of CCRL2-Mediated Chemerin Presentation.Journal of chemical information and modeling · 2025Article
- The Interplay Between Obesity and Venous Thromboembolism: From Molecular Aspects to Clinical Issue.International journal of molecular sciences · 2025Review
- Hair Calcium Levels in Relation to Coronary Artery Disease Severity and Systemic Inflammation Markers: A Pilot Study.Journal of clinical medicine · 2025Article
- Chemerin as a Driver of Cardiovascular Diseases: New Perspectives and Future Directions.Biomedicines · 2025Review
- Targeted drug delivery systems for atherosclerosis.Journal of nanobiotechnology · 2025Review
- Dysregulated cholesterol uptake and efflux of bone marrow-derived α-SMACellular and molecular life sciences : CMLS · 2025Article
- Endothelial IGFBP6 suppresses vascular inflammation and atherosclerosis.Nature cardiovascular research · 2025Article
- Decoding interaction between mitochondria and endoplasmic reticulum in ischemic myocardial injury: targeting natural medicines.Frontiers in pharmacology · 2025Review
- Chemerin in the Spotlight: Revealing Its Multifaceted Role in Acute Myocardial Infarction.Biomedicines · 2024Review
- Immune disease dialogue of chemokine-based cell communications as revealed by single-cell RNA sequencing meta-analysis.Frontiers in systems biology · 2024Article
- Constructing a competitive endogenous RNA network of EndMT-related atherosclerosis through weighted gene co-expression network analysis.Frontiers in cardiovascular medicine · 2023Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsChemoattractants and their cognate receptors are essential for leucocyte recruitment during atherogenesis, and atherosclerotic plaques preferentially occur at predilection sites of the arterial wall with disturbed flow (d-flow). In profiling the endothelial expression of atypical chemoattractant receptors (ACKRs), we found that Ackr5 (CCRL2) was up-regulated in an endothelial subpopulation by atherosclerotic stimulation. We therefore investigated the role of CCRL2 and its ligand chemerin in atherosclerosis and the underlying mechanism. METHODS AND
resultsBy analysing scRNA-seq data of the left carotid artery under d-flow and scRNA-seq datasets GSE131776 of ApoE-/- mice from the Gene Expression Omnibus database, we found that CCRL2 was up-regulated in one subpopulation of endothelial cells in response to d-flow stimulation and atherosclerosis. Using CCRL2-/-ApoE-/- mice, we showed that CCRL2 deficiency protected against plaque formation primarily in the d-flow areas of the aortic arch in ApoE-/- mice fed high-fat diet. Disturbed flow induced the expression of vascular endothelial CCRL2, recruiting chemerin, which caused leucocyte adhesion to the endothelium. Surprisingly, instead of binding to monocytic CMKLR1, chemerin was found to activate β2 integrin, enhancing ERK1/2 phosphorylation and monocyte adhesion. Moreover, chemerin was found to have protein disulfide isomerase-like enzymatic activity, which was responsible for the interaction of chemerin with β2 integrin, as identified by a Di-E-GSSG assay and a proximity ligation assay. For clinical relevance, relatively high serum levels of chemerin were found in patients with acute atherothrombotic stroke compared to healthy individuals.
conclusionsOur findings indicate that d-flow-induced CCRL2 promotes atherosclerotic plaque formation via a novel CCRL2-chemerin-β2 integrin axis, providing potential targets for the prevention or therapeutic intervention of atherosclerosis.
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