Effect of inflammatory cytokines on the metabolism of low-density lipoproteins by human vascular endothelial cells

Cytokines have been shown to activate multiple, varied metabolic pathways i n endothelial cells. Little information is available concerning the effects of inflammatory cytokines on lipoprotein metabolism by vascular endothelia l cells. Human umbilical vein endothelial cells (HuECs) and bovine aortic e ndothelial cells (BAECs) were incubated with the inflammatory cytokines rec ombinant human interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF) , interferon gamma (gamma -IF), and interferon beta (beta -IF) at increasin g concentrations (0.1 to 1,000 U/mL), for increasing periods (6 to 72 hours ), After the incubation period, the media were removed and replaced with se rum-free media containing radiolabeled native or acetylated low-density lip oprotein (Ac-LDL) and the rates of degradation and accumulation of radiolab eled LDL were determined. The degradation and accumulation of I-125-LDL wer e significantly increased (P < .02) in HuECs preincubated with IL-1 (100 U/ mL) compared with control incubations without the cytokine or incubations c ontaining <gamma>-IF, beta -IF, or TNF. This resulted from a 38% increase i n LDL receptor protein in cells incubated with IL-1. The increased rate of LDL catabolism by HuECs incubated with IL-l was accompanied by a significan t increase (P < .05) in the rate of cholesteryl ester synthesis in the cell s. Cholesteryl ester synthesis rates in HuECs preincubated with <gamma>-IF, beta -IF, or TNF did not differ significantly from the rates in control in cubations. The effect of preincubation with cytokine on the activity of the scavenger receptor was also determined. There were no significant differen ces in the rate of degradation or accumulation of radiolabeled Ac-LDL in co ntrol incubations compared with cultures preincubated with IL-1, gamma -IF, beta -IF, or TNF. There also were no significant differences in the rate o f catabolism of native LDL or Ac-LDL in BAECs preincubated with cytokines. Although cytokines have been shown previously to alter the binding of monoc ytes to endothelial cells, there was no significant increase in the binding of monocytes to cultures incubated with IL-1 plus LDL compared with IL-1 a lone, In summary, we now demonstrate that cytokines, specifically IL-1, may alter LDL metabolism by human vascular endothelial cells and alter endothe lial cell cholesterol metabolism. These changes in endothelial cell metabol ism provide additional evidence supporting the critical role of cytokines i n atherogenesis. Copyright (C) 2001 by W.B. Saunders Company.