CITED2 improves mitochondrial function in hypoxia/reoxygenation-induced human umbilical vein endothelial cells

doi:10.16352/j.issn.1001-6325.2026.08.1109

Abstract

Abstract: Objective To explore the role of CBP/p300-interacting transactivator 2 with Glu/Asp rich carboxy-terminal domain 2(CITED2) in patients with coronary slow blood flow (CSF) and its regulatory mechanism on endothelial cell hypoxia-reoxygenation (H/R) injury. Methods Peripheral blood samples were collected from CSF patients and healthy controls. Serum TNF-α, IL-6 and ROS levels were detected by ELISA, and the expressions of CITED2, hypoxia-inducible factor-1 α(HIF-1α), Dynamin-related protein 1(DRP1), Sirtuin 1(SIRT1) and Mitofusin 2(MFN2) in peripheral blood mononuclear cells (PBMCs) were analyzed by RT-qPCR and Western blot. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro to construct an H/R model, and the expression of CITED2 was regulated by transfection of siRNA and overexpression plasmid. The experiment was divided into control group, H/R group, H/R+OE-NC group, H/R+OE-CITED2 group, H/R+siNC group and H/R+siCITED2 group. The intracellular ROS level and mitochondrial membrane potential were detected by DHE and JC-1 staining, and the expression of related genes and proteins was detected by RT-qPCR and Western blot. Results Compared with the control group, the levels of TNF-α, IL-6 and ROS in CSF patients were significantly increased(P＜0.05), the expressions of HIF-1α and DRP1 in PBMCs were upregulated, and the expressions of CITED2, SIRT1 and MFN2 were down-regulated(P＜0.05). In HUVECs, the expression of HIF-1α and DRP1 increased significantly after H/R treatment, while the expression of CITED2, SIRT1 and MFN2 decreased. Overexpression of CITED2 significantly inhibited the expression of HIF-1α and DRP1, upregulate SIRT1 and MFN2, reduce ROS production and restore mitochondrial membrane potential. Knockdown of CITED2 aggravated the above damage effect. Conclusions CITED2 can reduce ROS production and restore mitochondrial membrane potential by regulating the expressions of HIF-1α, DRP1, SIRT1 and MFN2, thus improving the endothelial cell injury associated with CSF.

Key words: coronary slow flow, CITED2, hypoxia-reoxygenation injury, mitochondrial function

CLC Number:

R542.2

SUN Lihua, SHI Siyan, WANG Weihao, YANG Li, ZHANG Peidong. CITED2 improves mitochondrial function in hypoxia/reoxygenation-induced human umbilical vein endothelial cells[J]. Basic & Clinical Medicine, 2026, 46(8): 1109-1116.

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