Ang-Ⅱ介导的铁死亡参与房颤触发及心衰进展的机制研究OACSTPCD

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 ex-pression 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 stai-ning.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 in-tensity 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.