SR1001 confers protection against the experimental abdominal aortic aneurysm induced by angiotensin II in ApoE-/-mice

Abstract

Objective To investigate the effect and mechanism of SR1001 treatment in angiotensin Ⅱ (AngⅡ) induced experimental abdominal aortic aneurysm (EAAA) in apolipoprotein E (ApoE-/-) mice. Methods Forty-five male apolipoprotein E-deficient (ApoE-/-) mice were randomly divided into the following 3 groups: Sham group, AngⅡ model group (Control group), AngⅡ+ SR1001 treatment group (SR1001 group). All mice were treatment with 0.5% dimethylsurfoxide (DMSO) or SR1001 by intraperitoneal injection. The aortic diameter was measured via ultrasound imaging, and the suprarenal aorta was chosen as the measuring point on days 0, 14, 28 thereafter. Twenty-eight days after AngⅡ infusion, the abdominal aortic specimens were harvested. The elastica van Gieson (EVG) staining, and immunofluorescent staining were performed for histopathologic analysis. The protein levels of interleukin (IL)-17, monocyte chemotactic protein (MCP)-1, interferon (IFN)-γ were determined by Western blotting analysis. Results (1) Compared with the Control group, the AAA incidence in the SR1001 group was significantly reduced (33.3% vs. 73.3%, χ2=4.821, P=0.028), Abdominal aorta diameter [(1.39±0.06) mm vs. (1.98±0.11) mm, P=0.009]. However, there was no significant difference in abdominal aorta diameter between the SR1001 group and Sham group [(1.39±0.06) mm vs. (1.07±0.08) mm, P=0.064]. (2) SR1001 treatment in SR1001 group preserves the structure of the aortic wall (P=0.018). (3) SR1001 treatment in SR1001 group attenuates local inflammatory cell infiltration in the EAAA model. (4) SR1001 treatment in SR1001 group suppresses the protein expression of pro-inflammatory mediators (IL-17, MCP-1, IFN-γ) in the EAAA model (P=0.008, 0.016, 0.023, respectively). Conclusion Treatment with SR1001 inhibits the Th17/IL-17A-related inflammatory responses, preserves the structure of the aortic wall, reduces local inflammatory cell infiltration and inflammatory factors expression, and attenuates the progression of abdominal aortic aneurysm. Key words: SR1001; Angiotensin Ⅱ; Apolipoprotein E-/-mice; Interleukin-17; Inflammatory cell; Experimental abdominal aortic aneurysm