Platelet-derived Lrg1 links lung signaling to inflammatory remodeling of the aortic wall during aortic aneurysms [scRNA-Seq]

Here, we demonstrate that platelets and thrombopoiesis regulate aortic wall integrity in abdominal aortic aneurysms (AAA), a life-threatening disease marked by progressive dilation and rupture of the aorta. Aneurysmal platelets were enriched in Lrg1, which acted as a key effector coupling platelet activation to maladaptive matrix remodeling within the aortic wall.

Using lineage tracing, we found that bone marrow–derived Lrg1⁺ platelets accumulated during later stages of disease, whereas lung-derived Lrg1⁺ platelets were rapidly deployed to the abdominal aorta immediately after aneurysm induction and persisted throughout AAA progression, revealing an early and sustained crosstalk axis between the lungs and the vasculature. Conditional deletion of Lrg1 in platelets, as well as lung-specific suppression of Lrg1, protected mice from AAA, demonstrating that Lrg1 is a dominant molecular mediator through which lung-derived signals drive vascular remodeling.