2. Academic Validation
  3. MiR-1909-5p targeting GPX4 affects the progression of aortic dissection by modulating nicotine-induced ferroptosis

MiR-1909-5p targeting GPX4 affects the progression of aortic dissection by modulating nicotine-induced ferroptosis

  • Food Chem Toxicol. 2024 Jun 17:114826. doi: 10.1016/j.fct.2024.114826.
Yan Tao 1,  Gang Li 2,  Zhibin Wang 1,  Shizhong Wang 3,  Xingang Peng 4,  Guozhang Tang 1,  Xiaolu Li 1,  Jianhua Liu 5,  Tao Yu 6,  Xiuxiu Fu 7
Affiliations

Affiliations

  • 1 Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China.
  • 2 Department of Vascular Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong 250021, China; Department of Vascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, People's Republic of China.
  • 3 The department of Cardiology surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China.
  • 4 The department of emergency general surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China.
  • 5 Ultrasound medicine department, Guangzhou First People's Hospital, Guangzhou 510000, People's Republic of China;. Electronic address: eyliujianhua@scut.edu.cn.
  • 6 Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China;; Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People's Republic of China. Electronic address: yutao0112@qdu.edu.cn.
  • 7 Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China;. Electronic address: fuxiuxiu@qduhospital.cn.
PMID: 38897284 DOI: 10.1016/j.fct.2024.114826
Abstract

Objective: Aortic dissection (AD) is a prevalent and acute clinical catastrophe characterized by abrupt manifestation, swift progression, and elevated fatality rates. Despite smoking being a significant risk factor for AD, the precise pathological process remains elusive. This investigation endeavors to explore the mechanisms by which smoking accelerates AD through Ferroptosis induction.

Methodology: In this novel study, we detected considerable endothelial cell death by Ferroptosis within the aortic inner lining of both human AD patients with a smoking history and murine AD models induced by β-aminopropionitrile, angiotensin II, and nicotine. Utilizing bioinformatic approaches, we identified MicroRNAs regulating the expression of the Ferroptosis inhibitor Glutathione Peroxidase 4 (GPX4). Nicotine's impact on Ferroptosis was further assessed in human umbilical vein endothelial cells (HUVECs) through modulation of miR-1909-5p. Additionally, the therapeutic potential of miR-1909-5p antagomir was evaluated in vivo in nicotine-exposed AD mice.

Findings: Our results indicate a predominance of Ferroptosis over Apoptosis, Pyroptosis, and Necroptosis in the aortas of AD patients who smoke. Nicotine exposure instigated Ferroptosis in HUVECs, where the miR-1909-5p/GPX4 axis was implicated. Modulation of miR-1909-5p in these cells revealed its regulatory role over GPX4 levels and subsequent endothelial Ferroptosis. In vivo, miR-1909-5p suppression reduced Ferroptosis and mitigated AD progression in the murine model.

Conclusions: Our data underscore the involvement of the miR-1909-5p/GPX4 axis in the pathogenesis of nicotine-induced endothelial Ferroptosis in AD.

Keywords

GPX4; aortic dissection; endothelial cells; miR-1909-5p; nicotine.

Figures
Products