Huang Chenglin, Gao Jing, Wei Tong, Shen Weili
Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Rejuvenation Res. 2022 Feb;25(1):30-38. doi: 10.1089/rej.2021.0054. Epub 2022 Jan 28.
Oxidative stress may be an important cause of erythrocyte senescence. Angiotensin II (Ang II) has recently been shown to promote vascular cell senescence. However, its effects on erythrocytes remain unclear. This study aims at investigating the role of Ang II in regulating erythrocyte lifespan through oxidative stress. Experiments were performed in C57/BL6J mice infused with Ang II (1500 ng/kg per minute) or saline for 7 days. After Ang II infusion, we found that Ang II increased erythrocyte number, hemoglobin, and red blood cell distribution width. These differences were accompanied by a decrease in glutathione (GSH) and an increase in malondialdehyde (MDA) concentration. , after 24 hours of Ang II treatment, erythrocytes showed reduced surface expression of CD47 and increased phosphatidylserine exposure. In parallel, Ang II reduced the levels of antioxidant enzymes, including Cu/ZnSOD, catalase, and peroxidase 2 (PRDX2). These effects were reversed by the addition of the antioxidant N-acetyl-L-cysteine or the Ang II type 1 (AT1) receptor blocker losartan. In addition, Ang II treatment increased pro-inflammatory oxylipin, including hydroxyeicosatetraenoic acids (HETEs) and dihydroxyoctadecenoic acids (DiHOMEs), in the erythrocyte membranes. Collectively, Ang II induced erythrocyte senescence and susceptibility to eryptosis, partially due to enhanced oxidative stress.
氧化应激可能是红细胞衰老的一个重要原因。最近有研究表明血管紧张素II（Ang II）可促进血管细胞衰老。然而，其对红细胞的影响仍不清楚。本研究旨在探讨Ang II通过氧化应激在调节红细胞寿命中的作用。实验在C57/BL6J小鼠中进行，这些小鼠连续7天输注Ang II（每分钟1500 ng/kg）或生理盐水。输注Ang II后，我们发现Ang II增加了红细胞数量、血红蛋白和红细胞分布宽度。这些差异伴随着谷胱甘肽（GSH）的减少和丙二醛（MDA）浓度的增加。此外，Ang II处理24小时后，红细胞表面CD47表达降低，磷脂酰丝氨酸暴露增加。同时，Ang II降低了抗氧化酶的水平，包括铜/锌超氧化物歧化酶（Cu/ZnSOD）、过氧化氢酶和过氧化物酶2（PRDX2）。添加抗氧化剂N-乙酰-L-半胱氨酸或Ang II 1型（AT1）受体阻滞剂氯沙坦可逆转这些作用。此外，Ang II处理增加了红细胞膜中促炎氧化脂质的水平，包括羟基二十碳四烯酸（HETEs）和二羟基十八碳烯酸（DiHOMEs）。总体而言，Ang II诱导红细胞衰老和对红细胞凋亡的易感性，部分原因是氧化应激增强。
