VITAMIN-E INHIBITS LOW-DENSITY LIPOPROTEIN-INDUCED ADHESION OF MONOCYTES TO HUMAN AORTIC ENDOTHELIAL-CELLS IN-VITRO

Monocyte adhesion to human aortic endothelial cells (ECs) is one of th e early events in the development of atherogenesis. ECs were used to i nvestigate the role of vitamin E in human monocyte adhesion to ECs in vitro. ECs incubated with 40 to 193 mg/dL of low-density lipoprotein c holesterol (LDL) for 22 hours exhibited increasing dose-dependent adhe rence for untreated, isolated human monocytes (P<.05). ECs exposed to the highest dose of LDL (193 mg/dL) but pretreated with 19 mu mol/L al pha-tocopherol for 24 hours showed a trend to lower adherence for mono cytes compared with nontreated ECs (4.4+/-1.2% versus 7.6+/-1.9%; P=.0 9). This effect of vitamin E became more significant (P<.05) when ECs were exposed to a lower level of LDL (40 mg/dL) or were pretreated wit h a higher level of alpha-tocopherol (42 mu mol/L) and then exposed to 80 mg/dL LDL. Presupplementation of ECs with 15, 19, and 37 mu mol/L alpha-tocopherol significantly (P<.05) reduced monocyte adhesion by 6/-1%, 37+/-6%, and 69+/-17%, respectively. Levels of soluble intercell ular adhesion molecule-1 (sICAM-1), one of the adhesion molecules for monocytes, increased after incubation of ECs with LDL 80 mg/dL (4.7+/- 0.7 versus 6.4+/-1.2 ng/mL, respectively; P<.05). Treatment of ECs wit h alpha-tocopherol (42 mu mol/L) significantly reduced induction of sI CAM-1 by LDL to 2.2+/-2.3 ng/mL. After exposure to LDL, prostaglandin I-2 production by ECs was diminished, whereas presupplementation of EC s with alpha-tocopherol partially reversed the LDL effect. Production of interleukin-1 beta was not detectable when ECs were treated with al pha-tocopherol, LDL, or alpha-tocopherol followed by LDL. Our findings indicate that vitamin E has an inhibitory effect on LDL-induced produ ction of adhesion molecules and adhesion of monocytes to ECs via its a ntioxidant function and/or its direct regulatory effect on sICAM-1 exp ression.