DOI: https://doi.org/10.21203/rs.3.rs-2722286/v1
Objective: C1q/tumor necrosis factor-related protein 13 (CTRP13) preserves endothelial function and possesses anti-oxidation activity. However, its effects on human umbilical vein endothelial cells (HUVECs) ferroptosis remain unclear.
Methods: Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell viability. LDH assay and Malondialdehyde (MDA) were performed to evaluate the cell membrane integrity and lipid peroxidation. Mito-Tracker, JC-1, and 2′,7′-dichlorofluorescein di-acetate (DCFH-DA) were used to evaluate the biological activity of mitochondria, mitochondrial membrane potential, and reactive oxygen species (ROS) in endothelial cells. The ferroptosis indicator expressions, SLC7A11, GPX4, and ACSL4, were examined using real-time PCR and western blot. Immunofluorescence staining was used to detect GPX4 location in endothelial cells.
Results: This study identified a novel anti-atherosclerotic mechanism of CTRP13 inhibiting HUVECs ferroptosis by activating AMPK/KLF4 pathway. The cellular and database levels demonstrated that CTRP13 increased AMPK phosphorylation with subsequent restoration of the elevated KLF4.
Conclusion: These findings provided reliable data on the underlying mechanism of a newly identified adipokine to protect against atherosclerosis.