Figure 6. Anti-miRNA 125b decreased Mac3 expression, MMP expression, apoptosis and loss of SMCs in aorta from Ang II-infused ATP7A^mut/+/ApoE^−/− mice.

Abdominal aorta tissues from ApoE^−/− or ATP7A^mut/+/ApoE^−/− mice following 4 weeks of Ang II infusion with or without anti-miRNA 125b treatment were examined. A, Representative images of immunohistochemical staining for macrophages (Mac3) and quantification (n=4). Scale bars: 20 μm. B, Expression profiles of inflammatory genes by real-time qPCR (n=4). C, Immunohistochemical staining for MMP2 (top) and MMP9 (middle) and representative images of elastin integrity (bottom) and quantification (right) (n=4). D, Representative zymogram (top) of pro-MMP-2 and pro-MMP-9 levels and quantification (right). Scale bars: 20 μm. *p<0.05. E, Proposed model for the protective role of ATP7A against inflammation and smooth muscle cell apoptosis in experimental aortic aneurysm. ATP7A downregulation promotes AA formation by increasing vascular inflammation, in part via inducing miR-125b, thereby increasing MMP activity, elastin fragmentation, vascular apoptosis, and VSMC loss,. Thus, ATP7A is a potential therapeutic target for inflammatory vascular disease.