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| Mechanism Study on Ang -Ⅱ Mediated Ferroptosis in Triggering Atrial Fibrillation and Progression of Heart Failure |
| WANG Xinting, XU Mengmeng, KONG Xue, et al |
| Jining Third People's Hospital / Jining Yanzhou District People's Hospital, Shandong Jining 272000, China |
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Abstract Objective: To investigate the role of lysine demethylase 5B(KDM5B)/ enhanced activated transcription factor 3(ATF3) signaling pathway in angiotensin Ⅱ (Ang-Ⅱ)-induced cardiac hypertrophy.Methods: Mouse cardiomyocytes HL-1 were divided into the following treatment groups: control group, Ang-Ⅱ group, Ang-Ⅱ+Lv-NC group, Ang-Ⅱ+Lv-KDM5B group and Ang-Ⅱ+LV-KDM5KD group. The expression of KDM5B and ATF3 protein in cells of each group was analyzed by protein blot. The intracellular levels of α -actin (α-SMA), Fe2+ and reactive oxygen species (ROS) were detected by fluorescence staining. Results: Compared with Ang-Ⅱ+Lv-NC group, the expression of KDM5B protein in HL-1 cells in Ang-Ⅱ+Lv-KDM5B group increased significantly (P<0.05), and the expression of ATF3 protein decreased significantly (P<0.05), while the expression of KDM5B protein in HL-1 cells in Ang-Ⅱ+Lv-KDM5B KD group decreased significantly (P<0.05). Compared with the control group, the relative cell size, intracellular relative Fe2+ fluorescence intensity and relative ROS fluorescence intensity in Ang-Ⅱ group and Ang-Ⅱ+Lv-NC group increased significantly (P<0.05), and the relative cell viability decreased significantly (P<0.05). Compared with Ang-Ⅱ+Lv-NC group, the relative cell size, intracellular relative Fe2+ fluorescence intensity and relative ROS fluorescence intensity in Ang-Ⅱ+Lv-KDM5B group increased significantly (P<0.05), while the relative cell size, intracellular relative Fe2+ fluorescence intensity and relative ROS fluorescence intensity in Ang-Ⅱ+Lv-KDM5B KD group decreased significantly (P<0.05).Conclusion: KDM5B/ATF3 drives the progress of Ang-Ⅱ-induced myocardial hypertrophy and promotes ferroptosis related to hypertrophic stress response.
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2024, Vol. 30 
