Topiramate Attenuates Experimental Abdominal Aortic Aneurysm Via Modulating Macrophage Polarization

Background: The development of abdominal aortic aneurysm(AAA)is attributed to psychological and physical factors.Topiramate,which is an agonist of the GABA A receptor,significantly contributes to neuronal disease and is partially involved in immune regulation,may be effective against AAA.Objective: To investigate the role and machnism of GABA-A in abdominal aortic aneurysmMethods: We used experimental AAA models: Angiotensin II(Ang II)–induced Apo E-/-male mice(Ang II/APOE model)in our study.In the Ang II/APOE model,all mice(n=64)were divided into 4 groups: sham group(PBS treatment),control group(Ang II treatment),low-dose group(Ang II + low-dose topiramate,3 mg/d per mouse),and high-dose group(Ang II + high-dose topiramate,6mg/d per mouse).All treatments began on day 0 after surgery.Moreover,collected tissues and cultured cell were used for histology and biochemical examination.Results: Our data implied that topiramate treatment significantly promoted macrophages preservation and conversion of M1 to M2 macrophage phenotypes in vivo and vitro.Accordingly,pro-inflammatory 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 AAA incidences of 50% and 37.5%,respectively,compared with 75% in the control group.Conclusion: Topiramate,a promising drug for the psychological disease,that target neuro-immune-induced macrophage polarization can attenuate experimental AAA progression.This finding opens a new avenue for therapy of the cardiovascular disease from the neuro-immune dialog.