Pharmacological and genetic inhibition of BTK ameliorates vascular degeneration, dissection, and rupture.

Abstract

AIMS: Aortic aneurysm and dissection (AAD) involves complex immune responses, with macrophages playing a central role in vascular inflammation and AAD progression. The aim of this study was to determine the role of Bruton's tyrosine kinase (BTK) in macrophage-mediated inflammation and its impact on AAD progression. MAIN METHODS: We employed pharmacological and genetic approaches to inhibit BTK in AAD models induced by β-aminopropionitrile (BAPN) and angiotensin II (Ang II). Histological analysis, RNA sequencing, and molecular assays were used to assess macrophage polarization, inflammatory responses and progression of AAD. KEY FINDINGS: BTK was upregulated in both aortic tissue from patients undergoing surgery for aortic dissection and AAD mice model. BTK inhibition significantly reduced macrophage infiltration, modulated macrophage polarization, and attenuated AAD progression by limiting vascular inflammation. SIGNIFICANCE: These findings establish BTK as a key regulator of macrophage-driven vascular inflammation and a promising therapeutic target for AAD.