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.
Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113177. doi: 10.1016/j.intimp.2024.113177. Epub 2024 Sep 18.
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.
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).
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.
Angiotensin1-7 pretreatment inhibited vascular endothelial cells' ferroptosis and alleviated ECMO vessel injury through NF-κB /P53 signal pathway.
血管紧张素 1-7（Ang1-7）是血管紧张素 II 的经典终产物，具有扩张血管、保护内皮细胞、抗高血压、改善心功能和抑制动脉粥样硬化的作用。我们假设 Ang1-7 通过 NF-κB/P53 信号通路抑制人脐静脉内皮细胞（HUVEC）铁死亡，从而减少体外膜肺氧合（ECMO）血管损伤。
将培养的 HUVEC 种入 15 孔板中，并随机分为五组：对照组和四组实验组（依拉司琼、依拉司琼+Ang1-7、依拉司琼+Ang1-7+白桦脂酸、依拉司琼+白桦脂酸）。刺激后，测量细胞活力、乳酸脱氢酶（LDH）、丙二醛（MDA）和超氧化物歧化酶（SOD）活性。检测 Ang1-7 对 HUVEC 超微结构、抗氧化酶（铁蛋白重链 1（FTH1）、胱氨酸/谷氨酸反向转运溶质载体家族 7 成员 11（SLC7A11 或 XCT）、超氧化物歧化酶-2（SOD-2）和谷胱甘肽过氧化物酶 4（GPX4））、NF-κB、P-NF-κB、P53 和 P-P53 的影响。
依拉司琼刺激促进 HUVEC 脂质过氧化，降低抗氧化酶表达，增加 P-NF-κB、P53 和 P-P53 表达，破坏 HUVEC 线粒体结构。白桦脂酸预处理可减轻 Ang1-7 对依拉司琼破坏的 HUVEC 的作用。
血管紧张素 1-7 预处理通过 NF-κB/P53 信号通路抑制血管内皮细胞铁死亡，减轻 ECMO 血管损伤。
