From inflammation to degeneration: role of MMPs, IL6, and TIMP-1 in systemic sclerosis and aortic dissection.

Abstract

OBJECTIVE: To explore the susceptibility to aortic dissection in an SSc mouse model and identify potentially related markers. METHODS: Thirty-six female BALB/C mice were divided into experimental, control, and intervention groups (12 each). SSc was induced in the experimental and intervention groups using bleomycin, while the control group received phosphate-buffered saline. The intervention group additionally received MMP inhibitor SD1776. All groups were then subjected to angiotensin II injections to induce aortic dissection. Histopathological changes in the aortic wall and MMP expression levels were analysed using immunohistochemistry and western blotting. RESULTS: Mice with induced SSc showed more severe non-inflammatory degenerative changes in the aortic media, indicating increased susceptibility to aortic dissection. The experimental group exhibited higher MMP expression (MMP9, MMP2) compared to the intervention and control groups(&#x2009;<&#x2009;0.05). However, there was no significant difference in IL6 expression among the groups(&#x2009;>&#x2009;0.05). TIMP-1 expression was significantly higher in both the SSc and intervention groups compared to the control group(&#x2009;<&#x2009;0.05), suggesting a compensatory response to increased MMP activity. CONCLUSIONS: Mice with SSc were more prone to aortic dissection, potentially due to enhanced MMP activity in the aortic wall, underlining the importance of MMPs in the pathogenesis of aortic dissection in connective tissue diseases and indicating a pathway for future therapeutic interventions by targeting MMPs to mitigate the risk of aortic dissection in patients with SSc.