A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

Abdominal Aortic aneurysm (AAA) is connected with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a singular potent STAT3 inhibitor, continues to be lately reported to considerably block inflammation-related signaling pathways of JAK2/STAT3 and NF-?B, in addition to regulate autophagy. However, its role in vascular inflammation and AAA progression remains elucidated. In our study, the result and potential mechanisms of BP-1-102 on angiotensin II (AngII) caused AAA in ApoE-/- rodents were investigated. AAA was caused in ApoE-/- rodents with infusion of AngII for 4 weeks. BP-1-102 was administrated orally to rodents every second day. Rodents were sacrificed on day 7, day 14, and day 28 to judge the therapy effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of professional-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Furthermore, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-?B, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle tissues (VSMCs) were given AngII and/or BP-1-102 at indicated some time and concentration. BP-1-102 inhibited AngII-caused JAK2/STAT3 and NF-?B signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings claim that BP-1-102 inhibits vascular BP-1-102 inflammation and AAA progression through decreasing JAK2/STAT3 and NF-?B activation and looking after autophagy.