Bruton's Tyrosine Kinase Regulates Macrophage Polarization to Aggravate Progression of Aortic Aneurysm and Dissection

1. High levels of BTK expression were detected in aortic aneurysm patient samples and AAD mouse models. In the AAD model, BTK-/- mice showed significant reductions in challenge-induced aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions.2. The role of BTK in regulating inflammation in aortic aneurysms was analyzed by flow cytometry and RNA sequencing, the results show that BTK knockout improves AAD formation by inhibiting macrophage M1 phenotype and alleviating inflammatory response.3. The application of BTK-deficient mice in two models of AAD, complemented by macroscopic imaging, in vivo ultrasound assessments, and immunohistochemical analysis, revealed that the inhibition of BTK significantly improves AAD prevention. Furthermore, pharmacological blockade of BTK activation was shown to partially mitigate the progression of AAD.