Summary: | 碩士 === 中國醫藥大學 === 營養學系碩士班 === 98 === Atherosclerosis is regarded as a chronic inflammatory disease and its etiology is multifactorial. Abnormal lipid metabolism, such as increases in LDL concentrations in the circulation and the enhanced oxidation of LDL, is critical for the initiation and development of atherosclerosis In the early pathological stage, oxidized LDL (ox-LDL) induced expression of numerous adhesion molecules on the surface of vascular endothelial cells, which leads to increasing leukocyte adhesion and infiltration into the vessel wall. In addition, ox-LDL promotes vascular smooth muscle cell proliferation. Isothiocyanates (ITC) are organosulfur compounds rich in cruciferous vegetables. Previous studies have indicated that ITC are effective on protecting cardiovascular functions, inducing phase II detoxification enzyme expression, and promoting cancer cell apoptosis. In this study, we intend to elucidate the effect of benzyl isothiocyanate (BITC), phenylethyl isothiocyanate (PEITC) and sulforaphane (SFN) on ox-LDL-induced E-selectin expression in vascular endothelial cells and the molecular mechanisms involved. HUVEC were pretreated with 5 μM of BITC, PEITC or SFN for 24 h followed by exposing to 40 μg/ml ox-LDL for an additional 24 h. The results showed that (1) BITC, PEITC, and SFN pretreatment were effective on inhibiting ox-LDL-induced E-selectin expression; (2) three ITCs reduced the adherence of HL-60 to HUVEC; (3) intracellular heme oxygenase-1 (HO-1) expression was up-regulated by BITC, PEITC and SFN; (4) increase of intracellular reactive oxygen species (ROS) production by ox-LDL was suppressed by BITC, PEITC and SFN; (5) SFN significantly inhibited ox-LDL-induced ERK phosphorylation. Conclusion, results suggest that BITC, PEITC and SFN are effective on inducing HO-1 expression and, thus, ameliorating oxidative stress induced by ox-LDL, which in turn inhibit ERK activation and, finally, the expression of E-selectin in vascular endothelial cells.
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