Platelet ACKR3/CXCR7 surface expression is increased and impacts prognosis in individuals with coronary artery disease (CAD), who have an atherothrombotic platelet lipidome. For a study, researchers sought to verify the role of ACKR3/CXCR7 in modulating thromboinflammatory response via its effect on the platelet lipidome. Patients with CAD who had higher platelet ACKR3/CXCR7 expression had lower aggregation. Ex vivo, a pharmacological CXCR7 agonist (VUF11207) dramatically decreased prothrombotic platelet reactivity in blood from patients with the acute coronary syndrome. In vivo, treatment of a CXCR7 agonist decreased thrombotic activities and thrombo inflammatory platelet leukocyte interactions following myocardial infarction and arterial damage. ACKR3/CXCR7 ligation had no effect on surface receptor availability, coagulation profile, bleeding time, plasma-dependent thrombin generation (thrombinoscopy), or clot formation (thromboelastography), but it did inhibit activation-induced phosphatidylserine exposure and procoagulant platelet-assisted thrombin generation. 

In healthy subjects, ACKR3/CXCR7 ligation favored the generation of antithrombotic lipids (dihomo—linolenic acid [DGLA], 12-hydroxyeicosatrienoic acid [12-HETrE]) over COX-1 or 12-lipoxygenase (12-LOX) metabolized prothrombotic and phospholipase-derived atherogenic lipids. The ACKR3/CXCR7 ligation coordinated with the Gs-coupled prostacyclin receptor to cause platelet inhibition via cyclic adenosine monophosphate/protein kinase A. Ligation of the ACKR3/CXCR7 receptor lowered the production of lipid agonists and signaling intermediates, affecting calcium mobilization, intracellular signaling, and, as a result, platelet interaction with physiological matrices and the thrombo inflammatory secretome. The functional distinction between it and prothrombotic CXCR4 was highlighted as a result. In addition, ex vivo, CXCR7 agonist regulated heparin-induced thrombocytopenia–sera/immunoglobulin G–triggered platelet and neutrophil activation, heparin-induced platelet aggregation, generation of thrombo inflammatory lipids, platelet-neutrophil aggregate formation, and thrombo inflammatory secretions.

As a result, ACKR3/CXCR7 might be a unique treatment method for exacerbated cardiovascular diseases and CAD caused by acute/chronic thromboinflammation.

Reference:ashpublications.org/blood/article-abstract/139/11/1722/483060/Platelet-ACKR3-CXCR7-favors-antiplatelet-lipids?redirectedFrom=fulltext