• Birun Huang, Haiyan Chen, and Xiulan Zhang.
• Department of Vascular Surgery, the First Affiliated Hospital of Yangtze University, the First People's Hospital of Jingzhou, Jingzhou City, Hubei, China.
• Shock. 2025 Feb 1; 63 (2): 320326320-326.

AbstractBackground: Eugenol 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. Methods: Vascular smooth muscle cells (VSMCs) were pretreated 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 assay, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry. Inflammatory factors were examined by ELISA. Fe 2+ , glutathione, and malondialdehyde 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 assay and dual-luciferase reporter assay. Results: Eugenol 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. Conclusion: Eugenol 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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