KLF2 alleviates endothelial cell injury and inhibits the formation of THP‑1 macrophage‑derived foam cells by activating Nrf2 and enhancing autophagy.

Atherosclerosis (AS) is an important cause of common vascular diseases. The present study aimed to investigate whether Krüppel like transcription factor 2 (KLF2) could protect against endothelial cell injury and promote cholesterol excretion from foam cells through autophagy. An in vitro AS model was established by the induction of oxidized low-density lipoprotein (ox-LDL) for human umbilical vein endothelial cells (HUVECs). Phorbol-12-myristate-13-acetate (PMA)-induced THP-1 monocytes were differentiated into macrophages which were transformed to foam cells by ox-LDL incubation. The expression of KLF2, adhesion factors, cholesterol efflux regulatory proteins and autophagy-associated proteins in HUVECs or/and THP-1 monocytes was detected by reverse transcription-quantitative PCR and western blot analysis. HUVECs viability, levels of inflammatory factors, formation of foam cells and cholesterol efflux were respectively analyzed by CCK-8 assay, ELISA and Oil Red O staining. KLF2 expression was decreased in ox-LDL-induced HUVECs. KLF2 overexpression attenuated ox-LDL-induced endothelial cell injury, as evidenced by increased cell viability and decreased levels of TNF-α, IL-6, IL-1β, intercellular adhesion molecule 1, vascular cell adhesion molecule-1 and E-selectin. In addition, KLF2 overexpression inhibited the formation of THP-1 macrophage-derived foam cells and promoted lipid efflux. ox-LDL induced decreased KLF2 expression in THP-1 macrophage derived foam cells and KLF2 overexpression activated Nrf2 expression and enhanced autophagy. In conclusion, KLF2 alleviated endothelial cell injury and inhibited the formation of THP-1 macrophage-derived foam cells by activating Nrf2 and enhancing autophagy.