LOX-1 promotes hypoxia-induced autophagy and apoptosis in endothelial cells

doi:10.12092/j.issn.1009-2501.2025.08.002

Abstract

Abstract: AIM: To investigate the role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in hypoxia-induced autophagy and apoptosis in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to hypoxia (1%O₂) for varying durations (0, 6, 12, 24 h) to evaluate autophagy and apoptosis levels. LOX-1 was further intervened to explore its effects on autophagy and apoptosis. GFP-LC3B adenovirus infection was observed under fluorescence microscopy to assess LC3B expression. Autophagosomes were detected by transmission electron microscopy (TEM). LOX-1 mRNA levels were measured using real-time PCR. Protein expression of LOX-1, LC3II/I, Beclin-1, Atg5, cleaved-caspase 3, Bax, and Bcl-2 was analyzed by Western blot. Reactive oxygen species (ROS) levels were quantified using the DCFH-DA fluorescent probe. Apoptosis was assessed via Hoechst staining and flow cytometry (Annexin V-PI double staining). RESULTS: Hypoxia (1%O₂, 24 h) significantly increased LC3II puncta under fluorescence microscopy, upregulated LC3II/I protein expression, and induced autophagosome formation observed by TEM. Hypoxia elevated ROS production and promoted apoptosis. LOX-1 mRNA and protein expression were upregulated in hypoxic HUVECs. LOX-1 siRNA intervention markedly reversed hypoxia-induced autophagy, downregulating autophagy-related proteins (Beclin-1, Atg5, LC3II/I). LOX-1 siRNA also suppressed ROS generation and inhibited apoptosis, as evidenced by decreased expression of cleaved-caspase 3 and Bax, and increased Bcl-2 levels. CONCLUSION: Hypoxia induced upregulation of LOX-1 expression to produce ROS, thereby promoting autophagy and apoptosis in endothelial cells.

Key words: lectin-like oxidized low-density lipoprotein receptor-1, hypoxia, autophagy, apoptosis, endothelial cell

CLC Number:

R965.2

LI Yanfei¹, HUANG Can², LUO Ping³, HE Fang⁴, HU Changping². LOX-1 promotes hypoxia-induced autophagy and apoptosis in endothelial cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(8): 1017-1025.

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