Abstract
The development of abdominal aortic aneurysm (AAA) is attributed to psychological and physical factors. Topiramate, which is an agonist of the GABAA receptor, makes contributions to neuronal disease and is partially involved in immune regulation, may be effective upon abdominal aortic aneurysm progression. We used experimental abdominal aortic aneurysm models: Angiotensin II (Ang II)–induced ApoE−/− male mice (Ang II/APOE model) in our study. In the Ang II/APOE model, all mice (n=64) were divided into four groups: sham group (PBS treatment), control group (Ang II treatment), low-dose group (Ang II + low-dose topiramate, 3 mg/day per mouse), and high-dose group (Ang II + high-dose topiramate, 6 mg/day per mouse). All treatments began on the day after surgery. Moreover, collected tissues and cultured cell were used for histology and biochemical examination. In vitro, the effects of topiramate on bone marrow-derived macrophage stimulated by LPS were investigated. Our data implied that topiramate treatment significantly promoted macrophages preservation and conversion of M1 to M2 macrophage phenotypes in vivo and in vitro. Accordingly, proinflammatory activities mediated by the M1 macrophages were decreased and the repair process mediated by M2 macrophages was enhanced. The low-dose and high-dose groups had abdominal aortic aneurysm incidences of 50% and 37.5%, respectively, compared with 75% in the control group. Topiramate, a promising drug for the psychological disease, that target neuro-immune-induced macrophage polarization may attenuate experimental abdominal aortic aneurysm progression.
Highlights
With the rapidly growing aging population worldwide, abdominal aortic aneurysm (AAA) is becoming more prevalent in different countries and regions
By analyzing the ultrasound results and digital photographs of the aorta, we found that the AAA diameter of mice with high-dose topiramate treatment was significantly smaller than the control group, but there was no statistical significance between the control group and the low-dose group (Figures 3A, B, D)
We found that topiramate regardless of the high-dose group or the low-dose group markedly decreased the levels of MMP9, IL-1b, tumor necrosis factor-a (TNF-a), and iNOS in the peripheral blood by ELISA (Figure 5C)
Summary
With the rapidly growing aging population worldwide, abdominal aortic aneurysm (AAA) is becoming more prevalent in different countries and regions. AAA has been the third most major cause of cardiovascular death, about 1% to 3% of all deaths in males >65 years old (Sakalihasan et al, 2005). The incidence of AAA is on the rise, the mechanisms for the formation of aortic aneurysm remain unclear (Salmon et al, 2013; Yan et al, 2020). Except for surgery, few medical therapies can be used for confirmed AAA. The surgery typically is aimed at relatively large AAA rather than small or early stage AAA. As asymptomatic AAA can result in unpredictable fatal rupture (Powell and Greenhalgh, 2003), effective drugs preventing AAA dilation or protecting it from rupture are urgent to exploit
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