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Medical Science Monitor Basic Research


eISSN: 1643-3750

Upregulation of Nuclear Factor IA Suppresses Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Umbilical Vein Endothelial Cells

Zhenyu Zhou, Yu Chen, Wei Ni, Tao Liu

Department of Cardiology, Central Hospital of Nanchong, The Second Clinical School of North Sichuan Medical College, Nanchong, Sichuan, China (mainland)

Med Sci Monit 2019; 25:1009-1016

DOI: 10.12659/MSM.912132

Available online: 2019-02-05

Published: 2019-02-05


BACKGROUND: Endoplasmic reticulum stress (ERS) is part of the cardiovascular pathological processes, including atherosclerosis. Nuclear factor IA (NFIA) influences atherosclerosis development; however, its effects on ERS remain unknown. This study investigated the effect of NFIA on oxidized low-density lipoprotein (ox-LDL)-induced ERS and apoptosis in endothelial cells.
MATERIAL AND METHODS: Ox-LDL was used to induce lipotoxicity in human umbilical vein endothelial cells (HUVECs) to establish an in vitro oxidative injury model transfected with pcDNA3.0-NFIA. The cytotoxic response was detected using an assay to determine the release of lactate dehydrogenase (LDH). Morphological changes in cell apoptosis were detected using Hoechst 33258 staining. The proportion of apoptotic cells, releases of reactive oxygen species (ROS), and mitochondrial membrane potential (∆ψm) were determined using flow cytometry. The expression levels of apoptosis- and ERS-related molecules were detected through Western blotting.
RESULTS: NFIA expression was downregulated in the in vitro oxidative cell-injury model. Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis, decrease in ROS levels, and loss of ∆ψm. Overexpression of NFIA remarkably inhibited ERS and mitochondrial-mediated apoptosis induced by ox-LDL in HUVECs by reversing the effect of ox-LDL on the expression of JNK1, p-JNK1, CHOP, Cyt C, and Bax.
CONCLUSIONS: These results demonstrated that NFIA might have beneficial effects in the prevention of ox-LDL-induced ERS and apoptosis in vascular endothelial cells. This study provided new insights into the mechanism of atherosclerosis.

Keywords: atherosclerosis, Endoplasmic reticulum stress, endothelial cells