ArticleInternational journal of molecular sciences2020
CCL4 Inhibition in Atherosclerosis: Effects on Plaque Stability, Endothelial Cell Adhesiveness, and Macrophages Activation.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Association of CCL4 rs10491121 and rs1634507 gene polymorphisms with cancer susceptibility: trial sequential analysis and meta-analysis.Frontiers in oncology · 2023Pooled it
- Deciphering the interplay between SGLT2 inhibition, CCL4, and angina pectoris: A Mendelian randomization study.Medicine · 2026Article
- Article
- Association of Circulating C-C Motif Chemokine Ligand 4 to Disease Severity and Clinical Outcomes in Sepsis: A Prospective Observational Study.Biomedicines · 2026Article
- The role of chemokines and their receptors in cardiovascular diseases.Frontiers in immunology · 2026Review
- Lack of pathogenic involvement of CCL4 and its receptor CCR5 in arthritogenic alphavirus disease.ImmunoHorizons · 2025Article
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- IL1RAP Expression in Human Atherosclerosis: A Target of Novel Antibodies to Reduce Vascular Inflammation and Adhesion.Journal of the American Heart Association · 2025Article
- Inflammatory Responses to Zn/Cu-Containing Welding Fume in Human Alveolar Epithelial and Macrophage Cell Lines, with MIP-1β/CCL4 as a Much More Sensitive Macrophage Activation Marker than IL-8 and TNF-α.International journal of molecular sciences · 2025Article
- Plasma proteomics improves prediction of coronary plaque progression.European heart journal. Cardiovascular Imaging · 2025Article
- Chemokine Ligands and Receptors Regulate Macrophage Polarization in Atherosclerosis: A Comprehensive Database Mining Study.CJC open · 2025Article
- Novel therapeutic targets for metabolism-related diseases: proteomic Mendelian randomization and colocalization analyses.Therapeutic advances in endocrinology and metabolism · 2025Article
- Dichotomous roles of IL-36 and IL-38 in cardiovascular disease.Frontiers in immunology · 2025Review
- Integrated Analysis of Ferroptosis- and Cellular Senescence-Related Biomarkers in Atherosclerosis Based on Machine Learning and Single-Cell Sequencing Data.Journal of inflammation research · 2025Article
- Exploration of potential biomarkers and immune cell infiltration characteristics for peripheral atherosclerosis in sjögren's syndrome based on comprehensive bioinformatics analysis and machine learning.Frontiers in genetics · 2025Article
- Expression of CCL2 signaling pathway genes in patients with periodontitis and atherosclerosis.Histology and histopathology · 2024Article
- CCL4 contributes to aging related angiogenic insufficiency through activating oxidative stress and endothelial inflammation.Angiogenesis · 2024Article
- Novel biomarkers identified by weighted gene co-expression network analysis for atherosclerosis.Herz · 2024Article
- Deficiency of lncRNA MERRICAL abrogates macrophage chemotaxis and diabetes-associated atherosclerosis.Cell reports · 2024Article
- Deciphering the role of CCL4-CCR5 in coronary artery disease pathogenesis: insights from Mendelian randomization, bulk RNA sequencing, single-cell RNA, and clinical validation.International journal of medical sciences · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Atherosclerosis is an arterial inflammatory disease. The circulating level of the C-C chemokine ligand (CCL4) is increased in atherosclerotic patients. This study aimed to investigate whether CCL4 inhibition could retard the progression of atherosclerosis. In ApoE knockout mice, CCL4 antibody treatment reduced circulating interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α levels and improved lipid profiles accompanied with upregulation of the liver X receptor. CCL4 inhibition reduced the atheroma areas and modified the progression of atheroma plaques, which consisted of a thicker fibrous cap with a reduced macrophage content and lower matrix metalloproteinase-2 and -9 expressions, suggesting the stabilization of atheroma plaques. Human coronary endothelial cells (HCAECs) and macrophages were stimulated with TNF-α or oxidized LDL (ox-LDL). The induced expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were attenuated by the CCL4 antibody or CCL4 si-RNA. CCL4 inhibition reduced the adhesiveness of HCAECs, which is an early sign of atherogenesis. CCL4 blockade reduced the activity of metalloproteinase-2 and -9 and the production of TNF-α and IL-6 in stimulated macrophages. The effects of CCL4 inhibition on down-regulating adhesion and inflammation proteins were obtained through the nuclear factor kappa B (NFκB) signaling pathway. The direct inhibition of CCL4 stabilized atheroma and reduced endothelial and macrophage activation. CCL4 may be a novel therapeutic target for modulating atherosclerosis.
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Registered trials
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