2. Academic Validation
  3. Angiotensin 1-7 restrains vascular injury of extracorporeal membrane oxygenation by inhibiting ferroptosis

Angiotensin 1-7 restrains vascular injury of extracorporeal membrane oxygenation by inhibiting ferroptosis

  • Int Immunopharmacol. 2024 Dec 5;142(Pt B):113177. doi: 10.1016/j.intimp.2024.113177.
Shengqiang Li 1,  Yuping Wang 2,  Zhen Lv 3,  Qizhi Wang 2,  Tong Jia 4,  Zhenzhen Zhai 5,  Wei Fang 6
Affiliations

Affiliations

  • 1 The Affiliated Taian City Central Hospital of Qingdao University, 271000 Taian, China; Department of Physiology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 2 Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 3 Department of Cardiology, Zibo First Hospital, Zibo 255200, China.
  • 4 Department of Geratology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. Electronic address: bingchaningmeng@163.com.
  • 5 The Affiliated Taian City Central Hospital of Qingdao University, 271000 Taian, China. Electronic address: zhaizhen0901@163.com.
  • 6 Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. Electronic address: doctorfang@163.com.
PMID: 39298820 DOI: 10.1016/j.intimp.2024.113177
Abstract

Background: Angiotensin 1-7 (Ang1-7) is the classical end product of angiotensin II, which has the effects of dilating blood vessels, protecting endothelial cells, anti-hypertension, improving cardiac function, and inhibiting atherosclerosis. We hypothesize that Ang1-7 inhibits human umbilical vein endothelial cells (HUVEC) Ferroptosis through NF-κB/P53 signal pathway, and reduces extracorporeal membrane oxygenation (ECMO) vascular injury.

Methods: Cultured HUVEC were seeded into 15 wells and randomly divided into five groups: the control group and four experimental groups (erastin, erastin + Ang1-7, erastin + Ang1-7 + Betulinic acid, erastin + Betulinic acid). After stimulation, cell viability, Lactate Dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) activity were measured. The effects of Ang1-7 on HUVEC microstructure, antioxidant Enzymes (ferritin heavy chain 1 (FTH1), cystine/glutamic acid reverse transport solute carrier family 7 members 11 (SLC7A11 or XCT), superoxide dismutase-2 (SOD-2) and Glutathione Peroxidase 4 (GPX4)), NF-κB, P-NF-κB, P53, and P-P53).

Results: Erastin stimulation promoted HUVEC lipid peroxidation, decreased antioxidant Enzyme expression, increased P-NF-κB, P53, and P-P53 expressions, and damaged HUVEC mitochondrial structure. Ang1-7 alleviated the effect of erastin on HUVEC, which was destroyed by Betulinic acid.

Conclusion: Angiotensin1-7 pretreatment inhibited vascular endothelial cells' Ferroptosis and alleviated ECMO vessel injury through NF-κB /P53 signal pathway.

Keywords

Angiotensin1-7; ECMO; Ferroptosis; NF-κB; P53.

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