Targeted depletion of monocyte/macrophage suppresses aortic dissection with the spatial regulation of MMP-9 in the aorta

Publication date: Available online 29 October 2019Source: Life SciencesAuthor(s): Xue Li, Dan Liu, Lijie Zhao, Linlin Wang, Yuanmin Li, Kenka Cho, Chunlei Tao, Baohong JiangAbstractAimAortic dissection (AD) is a devastating disease with rapid progression and high mortality, while the initiation mechanism of AD is far from clear.Main methodsAD was established by feeding mice with β-aminopropionitrile in the diet and usage of angiotensin II (AngII) to trigger the rupture of aorta. LysMiDTR mice were constructed by crossing of LysM-Cre mice with ROSA26iDTR mice and characterized by diphtheria toxin receptor (DTR) expression in monocytes/macrophages specifically. Then, monocyte/macrophage depletion in LysMiDTR mice was conducted to evaluate the function of monocyte/macrophage in AD. Finally, the underlying mechanism was elucidated by proteomics, Western blot analysis, immunofluorescence staining and bioinformatics analysis.Key findingsFirst, we detected T lymphocytes, macrophages and neutrophils infiltrated into the aorta simultaneously when AD occurred, and macrophages were the most abundant cell type. Then, targeted depletion of monocyte/macrophage in LysMiDTR mice considerably inhibited the occurrence of AD and infiltration of T lymphocytes and neutrophils. Furthermore, monocyte transfusion into LysMiDTR mice augmented the rupture of aorta, jointly supporting the key roles of monocytes/macrophages in AD development. Mechanistically, a total of 347 proteins exhibited significa...
Source: Life Sciences - Category: Biology Source Type: research