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Updated: Jun 17, 2026

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
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Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation

Published on: May 23, 2025

Targeting ACKR3/CXCR7 Enhances Platelet Anticoagulant Acylcarnitines and Modulates Procoagulant Function

Xiaoqing Fu1, Adrian Brun2, Kristina Dittrich2

  • 1School of Medicine, Shanghai University, China.

Blood
|June 15, 2026
PubMed

Insights

Targeting ACKR3/CXCR7 with agonists reduces pro-thrombotic lipids and enhances anti-thrombotic lipids, improving platelet function and mitochondrial metabolism. This approach offers a novel strategy for managing thrombotic disorders.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cardiovascular Research
  • Hematology

Background:

  • ACKR3/CXCR7 plays a role in regulating lipid metabolism and platelet activation, which are critical in thrombotic processes.
  • Dysregulation of lipid processing and platelet function contributes to cardiovascular diseases like STEMI and venous thromboembolism (VTE).
  • Existing therapeutic strategies may not fully address the complex interplay between lipids, platelets, and coagulation.

Purpose of the Study:

  • To investigate the role of ACKR3/CXCR7 in modulating lipid metabolism, platelet function, and mitochondrial activity in the context of thrombosis.
  • To evaluate the therapeutic potential of pharmacological CXCR7 agonism in regulating pro-thrombotic and anti-thrombotic pathways.
  • To explore the impact of CXCR7 targeting on anticoagulatory lipid generation and hypercoagulation.

Main Methods:

  • Utilized a pharmacological CXCR7 agonist (VUF11207) in in vitro platelet studies and in vivo murine venous thrombosis models.
  • Assessed mitochondrial function (membrane integrity, superoxide generation, respiration), lipid (per)oxidation, and lipoprotein uptake.
  • Measured platelet activation markers (degranulation, integrin activation, aggregation), coagulation parameters (phosphatidylserine exposure, thrombin generation), and plasma mediator levels.

Main Results:

  • CXCR7 agonism preserved mitochondrial integrity, reduced oxidative stress and lipid peroxidation, and inhibited lipoprotein-induced platelet activation and aggregation.
  • Activation of the AMPK-ACC pathway by CXCR7 ligation promoted lipolysis and increased the generation of anti-thrombotic long-chain acylcarnitines (LC-CARs).
  • In vivo, CXCR7 agonist treatment reduced thrombus formation, inflammatory mediators, and procoagulant lipids while increasing plasma LC-CAR levels.

Conclusions:

  • Pharmacological targeting of CXCR7 effectively regulates lipid processing and promotes anticoagulatory LC-CAR generation, mitigating platelet-driven thrombotic propensity.
  • CXCR7 agonism offers a dual benefit by reducing pro-thrombotic factors and enhancing anti-thrombotic mechanisms, including sustained mitochondrial function.
  • This strategy holds promise for replenishing reduced anticoagulant levels in patients with STEMI and VTE, suggesting a novel therapeutic avenue.

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