Inflammation plays an important role in
aortic dissection (AD). Macrophages are critically involved in the
inflammation after aortic injury. Neuraminidases (NEUs) are a family of
enzymes that catalyze the cleavage of terminal
sialic acids from
glycoproteins or
glycolipids, which is emerging as a regulator of macrophage-associated immune responses. However, the role of
neuraminidase 1 (NEU1) in pathological
vascular remodeling of AD remains largely unknown. This study sought to characterize the role and identify the potential mechanism of NEU1 in pathological aortic degeneration. After β-
aminopropionitrile monofumarate (
BAPN) administration, NEU1 elevated significantly in the lesion zone of the aorta. Global or macrophage-specific NEU1 knockout (NEU1 CKO) mice had no baseline aortic defects but manifested improved aorta function, and decreased mortality due to
aortic rupture. Improved outcomes in NEU1 CKO mice subjected to
BAPN treatment were associated with the ameliorated vascular
inflammation, lowered apoptosis, decreased
reactive oxygen species production, mitigated extracellular matrix degradation, and improved M2 macrophage polarization. Furthermore, macrophages sorted from the aorta of NEU1 CKO mice displayed a significant increase of M2 macrophage markers and a marked decrease of M1 macrophage markers compared with the controls. To summarize, the present study demonstrated that macrophage-derived NEU1 is critical for vascular homeostasis. NEU1 exacerbates
BAPN-induced pathological
vascular remodeling. NEU1 may therefore represent a potential therapeutic target for the treatment of AD.