{"title":"Eugenol restrains Angiotensin II-induced death, inflammation and ferroptosis of vascular smooth muscle cells by targeting STAT3/HMGB2 axis.","authors":"Birun Huang, Haiyan Chen, Xiulan Zhang","doi":"10.1097/SHK.0000000000002498","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Vascular 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Eugenol could slow down the development of AAA, which might be achieved by regulating STAT3/HMGB2 axis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002498","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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 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.
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.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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