KLF2 alleviates endothelial cell injury and inhibits the formation of THP­1 macrophage­derived 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-1ß, 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.