Aneurysm Is Restricted by CD34+ Cell‐Formed Fibrous Collars Through the PDGFRb‐PI3K Axis

Abstract Aortic aneurysm is a life‐threatening disease caused by progressive dilation of the aorta and weakened aortic walls. Its pathogenesis involves an imbalance between connective tissue repair and degradation. CD34 + cells comprise a heterogeneous population that exhibits stem cell and progenitor cell properties. However, the role of CD34 + cells in abdominal aortic aneurysm (AAA) remains unclear. In this study, downregulated CD34 expression is observed in aneurysmal aortas from both patients and mouse models compared to that in non‐dilated aortas. Furthermore, by combining Cd34 ‐CreER T2 ;Rosa26‐tdTomato;( Apoe −/− ) lineage tracing, bone marrow transplantation, and single‐cell sequencing, it is found that during AAA development, non‐bone marrow CD34 + cells are activated to transdifferentiate into Periostin + myofibroblasts, thereby contributing to the formation of fibrotic collars. Dual recombinase‐based lineage tracing confirms the presence and involvement of CD34 + /Periostin + myofibroblasts in fibrotic collar formation during AAA development. Functionally, selective depletion of systemic or non‐bone marrow CD34 + cells, as well as CD34 + /Periostin + myofibroblasts, by diphtheria toxin significantly exacerbates AAA progression and increases disease mortality. Mechanistically, it is identified that the PDGF‐PDGFRb‐PI3K axis is indispensable for Periostin + myofibroblast generation from non‐bone marrow CD34 + cells in AAA, offering a new therapeutic target for patients with AAA at a high risk of rupture.