• Birun Huang, Haiyan Chen, and Xiulan Zhang.
• Department of Vascular Surgery, the First People's Hospital of Jingzhou, the First Affiliated Hospital of Yangtze University, Jingzhou City, 434000, Hubei, China.
• Shock. 2024 Oct 18.

BackgroundEugenol has been found to inhibit a variety of disease processes, including abdominal aortic aneurysm (AAA) formation. However, the specific role and the underlying molecular mechanism of Eugenol in AAA progression need to be further revealed.MethodsVascular smooth muscle cells (VSMCs) were pre-treated with Eugenol, followed by treated with Angiotensin II (Ang-II). VSMCs were transfected with HMGB2 siRNA or overexpression vector and treated with Ang-II to confirm the effect of HMGB2 on AAA progression. Cell proliferation and death were determined using cell counting kit 8 (CCK8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry. Inflammatory factors were examined by ELISA. Fe2+, glutathione (GSH) and malondialdehyde (MDA) levels were tested to evaluate cell ferroptosis. The protein levels of ferroptosis-related markers, high mobility group box 2 (HMGB2) and STAT3 were measured using western blot. Human AAA tissues and normal abdominal aortic tissues were collected to detect HMGB2 mRNA expression by quantitative real-time PCR. The interaction between HMGB2 and STAT3 was confirmed by chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter assay.ResultsEugenol enhanced VSMCs proliferation, while restrained Ang-II-induced death, inflammation and ferroptosis. HMGB2 was upregulated in AAA tissues and Ang-II-induced VSMCs, and Eugenol significantly decreased HMGB2 expression. HMGB2 knockdown reduced Ang-II-induced VSMCs death, inflammation and ferroptosis, Besides, HMGB2 overexpression abolished the effect of Eugenol on Ang-II-induced VSMCs injury. Transcription factor STAT3 bound to HMGB2 promoter region to increase its expression. In addition, Eugenol decreased STAT3 expression to regulate HMGB2.ConclusionEugenol could slow down the development of AAA, which might be achieved by regulating STAT3/HMGB2 axis.Copyright © 2024 by the Shock Society.

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