Targeting ACKR3/CXCR7 Enhances Platelet Anticoagulant Lipids and Modulates Procoagulant Function: Implications for Thrombosis Management

Highlight

• Activation of the atypical chemokine receptor CXCR7 (ACKR3) modulates platelet lipid processing, favoring anticoagulant long-chain acylcarnitines (LC-CAR) over prothrombotic lipids.
• CXCR7 agonist VUF11207 preserves mitochondrial integrity and reduces platelet oxidative stress, thereby limiting procoagulant platelet activation.
• The CXCR7-AMPK-ACC signaling axis promotes platelet lipolysis, reduces phosphatidylserine exposure, and diminishes FX/FXa binding, cumulatively reducing thrombin generation and thrombosis in vivo.
• Targeting CXCR7 in thrombosis models decreases inflammation and procoagulant lipid mediators, highlighting its therapeutic potential in cardiovascular conditions such as STEMI and venous thromboembolism (VTE).