Abstract
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.
Highlights
Aortic dissection (AD) is a fatal surgical emergency characterized by acute-onset chest or back pain with few, if any, preceding signs [1]
Since neuraminidase 1 (NEU1) was reported to highly expressed in macrophages in atherosclerosis vessels [20], we speculated that NEU1 may highly expressed in macrophages in aortic dissection (AD) vessels
We found that NEU1 expression was significantly upregulated in dissecting tissues from BAPN-induced AD mice
Summary
Aortic dissection (AD) is a fatal surgical emergency characterized by acute-onset chest or back pain with few, if any, preceding signs [1]. In addition to mutations in some genes involved in extracellular matrix metabolism and smooth muscle cytoskeleton, some highrisk factors for AD have been confirmed, including longterm hypertension, dyslipidemia, smoking, giant cell arteritis, etc. These non-genetic factors suggest that the inflammation may make the aorta susceptible to AD [6]. Inflammatory cells infiltrate the injured site of the aorta to remove necrotic cells and damaged tissue; the excessive inflammation may play a role in aneurysm formation after dissection [7]. An analysis of gene expression changes in human dissecting tissues using cDNA microarrays confirmed that the inflammation was involved in the pathogenesis of disease [9]. IL-6-STAT3 signaling pathway promotes AD induced by angiotensin (Ang) II via the Th17/IL-17 axis in mice [13]
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