Interplay Between Thrombospondin-1 and CD36 Modulates Platelet–RBC Interaction in Thrombosis and Abdominal Aneurysm Formation

作者：Kim Jürgen Krott, Tobias Feige, A Bosbach, Alicia Beele, Irena Krueger, Friedrich Reusswig, Elena Schickentanz-Dey, Susanne Pfeiler, Alexandra Chadt, Malte Kelm, Norbert Gerdes, Kerstin Jurk, Klytaimnistra Kiouptsi, Christoph Reinhardt, Hadi Al‐Hasani, Beate E. Kehrel, Saoussen Karray, Madhumita Chatterjee, Hubert Schelzig, Markus Udo Wagenhäuser, Margitta Elvers · 发表于：Circulation Research · 年份：2025 · DOI：10.1161/circresaha.125.326701 · 被引用次数：7 · 研究领域：Aortic aneurysm repair treatments、Angiogenesis and VEGF in Cancer、Platelet Disorders and Treatments

BACKGROUND: Red blood cells (RBCs) contribute to hemostasis and thrombosis by interacting with platelets via the FasL-FasR pathway to induce procoagulant activity and thrombin formation. Here, we identified a novel mechanism of platelet-RBC interaction via the CD36-TSP-1 (thrombospondin-1) signaling pathway that plays a prominent role in arterial thrombosis and abdominal aortic aneurysm (AAA) formation and progression. AAA is a life-threatening atherosclerotic-related disease, characterized by the progressive dilation of the abdominal aorta, due to chronic inflammation and extracellular matrix remodeling/degradation within the vessel wall. The objective of the present study was to elucidate a new mechanism of platelet-RBC interaction via the TSP1-CD36 axis and its significance for arterial thrombosis and the pathology of AAA. METHODS: TSP-1-deficient and CD36 cell-type-specific (RBCs and platelets) knock-out mice were analyzed in experimental mouse models of arterial thrombosis and AAA. Blood samples from patients with AAA from peripheral sites (laminar flow) and from inside the aneurysm segment (turbulent flow) were analyzed by flow cytometry and compared with age-matched controls. RESULTS: After platelet activation, platelet-released TSP-1 binds to CD36 at the RBC and platelet membrane to enhance procoagulant activity of both cells, leading to platelet aggregation and thrombosis. Patients with AAA exhibit enhanced procoagulant activity, elevated TSP-1 and CD36 plasma levels...