ArticleBlood2022
Targeting platelet-derived CXCL12 impedes arterial thrombosis.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The role of blood CXCL12 level in prognosis of coronary artery disease: A meta-analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- A scalable high-throughput platform for the discovery of intracellular and extracellular regulators of platelet migration.Blood advances · 2026Article
- Exosomal Protein Biomarkers for Predicting Early Neurological Deterioration Following Intravenous Thrombolysis in Acute Ischemic Stroke.Translational stroke research · 2026Article
- Radiation-activated astrocytes promote tumor progression through CXCL12 secretion and induce resistance to anti-PD-1 immunotherapy.Translational cancer research · 2026Article
- A panel of plasma proteins associated with venous thromboembolism in patients with prostate cancer.Cancer biomarkers : section A of Disease markers · 2025Article
- Alterations in the Platelet Transcriptome Mediate Prenatal Thirdhand Smoke Exposure Associated Thrombogenicity via Integrated miRNA-mRNA Regulatory Networks.International journal of molecular sciences · 2025Article
- Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits.Blood vessels, thrombosis & hemostasis · 2025Article
- ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function.European journal of clinical investigation · 2025Article
- Alterations in visible light exposure modulate platelet function and regulate thrombus formation.Journal of thrombosis and haemostasis : JTH · 2025Article
- Chemokines play a role in nerve damage and neuroprotection in vascular dementia.IBRO neuroscience reports · 2024Review
- Targeting immune cell recruitment in atherosclerosis.Nature reviews. Cardiology · 2024Review
- Comparative studies between humans and golden Syrian hamsters via thromboelastography.Animal models and experimental medicine · 2024Article
- Pim Kinase Inhibition Disrupts CXCR4 Signalling in Megakaryocytes and Platelets by Reducing Receptor Availability at the Surface.International journal of molecular sciences · 2024Article
- Platelet biology and function: plaque erosion vs. rupture.European heart journal · 2024Review
- Article
- CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway.Redox biology · 2023Article
- Chemokine Heteromers and Their Impact on Cellular Function-A Conceptual Framework.International journal of molecular sciences · 2023Review
- Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets.International journal of molecular sciences · 2023Article
- Platelets at the Vessel Wall in Non-Thrombotic Disease.Circulation research · 2023Review
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prevention and treatment of arterial thrombosis continue to be clinically challenging, and understanding the relevant molecular mechanisms in detail may facilitate the quest to identify novel targets and therapeutic approaches that improve protection from ischemic and bleeding events. The chemokine CXCL12 augments collagen-induced platelet aggregation by activating its receptor CXCR4. Here we show that inhibition of CXCR4 attenuates platelet aggregation induced by collagen or human plaque homogenate under static and arterial flow conditions by antagonizing the action of platelet-secreted CXCL12. We further show that platelet-specific CXCL12 deficiency in mice limits arterial thrombosis by affecting thrombus growth and stability without increasing tail bleeding time. Accordingly, neointimal lesion formation after carotid artery injury was attenuated in these mice. Mechanistically, CXCL12 activated via CXCR4 a signaling cascade involving Bruton's tyrosine kinase (Btk) that led to integrin αIIbβ3 activation, platelet aggregation, and granule release. The heterodimeric interaction between CXCL12 and CCL5 can inhibit CXCL12-mediated effects as mimicked by CCL5-derived peptides such as [VREY]4. An improved variant of this peptide, i[VREY]4, binds to CXCL12 in a complex with CXCR4 on the surface of activated platelets, thereby inhibiting Btk activation and preventing platelet CXCL12-dependent arterial thrombosis. In contrast to standard antiplatelet therapies such as aspirin or P2Y12 inhibition, i[VREY]4 reduced CXCL12-induced platelet aggregation and yet did not prolong in vitro bleeding time. We provide evidence that platelet-derived CXCL12 is involved in arterial thrombosis and can be specifically targeted by peptides that harbor potential therapeutic value against atherothrombosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.