Hepatocyte steatosis increases the expression of adhesion molecules in endothelial cells

Background: Non-alcoholic fatty liver disease is considered a hepatic manifestation of the metabolic syndrome. It is associated with endothelial dysfunction as an early event of generalized atherosclerosis. However, it is unclear whether steatotic hepatocytes influence endothelial function directly. Objective: Explore the influence of hepatocyte steatosis on the function of endothelial cells. Methods: Oleic and palmitic acid (2:1 mixture, final concentration: 1 mM for 24 hours) was used to induce a normal adult hepatocyte strain (L-02) for transformation into steatosis cells. This was followed by oil red O staining and transmission electron microscopy (TEM) for verification. The culture solution of steatotic L-02 cells was filtered and collected, and added into the culture substrate of human umbilical vein endothelial cells (HUVECs). The expression of vascular cellular adhesion molecule -1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in HUVECs was detected by real-time polymerase chain reaction and Western blot assays. The apoptosis and proliferation of HUVECs was determined using flow cytometry. The experimental results were compared with the controls. Results: Oil red O staining and microscopic observation showed that the cytoplasm of induced L-02 cells contained a large amount of red lipid droplets. TEM results showed that the cytoplasm had lipid accumulation, swelling mitochondria, fewer cristae, and reduced number of rough endoplasmic reticula accompanied with degranulation. However, these changes were not observed in normal L-02 cells. As to the group of HUVECs treated by the filtrate of steatosis L-02 cells, the mRNA and protein expression of VCAM-1, ICAM-1, and E-selectin was higher than that in the control group. The difference was statistically significant (p <0.01). No significant difference was found when HUVECs apoptosis and proliferation were assessed by flow cytometry. Conclusion: Secretion from steatotic hepatocytes could boost the expression of VCAM-1, ICAM-1, and E-selectin in endothelial cells, indicating that hepatocyte steatosis could induce endothelial cell dysfunction. The proliferation and apoptosis of endothelial cells did not change, suggesting that hepatocyte steatosis had no influence on the viability of endothelial cells under this condition.