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Increased circulating lipid peroxides in severe preeclampsia activate NF‐κΒ and upregulate ICAM‐1 in vascular endothelial cells
Author(s) -
Takacs P.,
Kauma S. W.,
Sholley M. M.,
Walsh S. W.,
Dinsmoor M. J.,
Green K.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0549fje
Subject(s) - preeclampsia , endocrinology , medicine , umbilical vein , oxidative stress , endothelial dysfunction , chemistry , malondialdehyde , vitamin e , biology , antioxidant , in vitro , biochemistry , pregnancy , genetics
Preeclampsia is a systemic disease of pregnancy characterized by maternal hypertension, proteinuria, and edema. These clinical pathological findings may be attributed to abnormalities in vascular endothelial activation secondary to increased oxidative stress. To test the hypothesis that increased circulating lipid peroxides in preeclamptic women activate vascular endothelial cells, we determined NF‐κΒ transcriptional activity and ICAM‐1 expression in human umbilical vein endothelial cells (HUVEC) cultured with plasma from women with severe preeclampsia (preeclamptic plasma, N = 12) or plasma from normal pregnancies (normal plasma, N = 12). Preeclamptic women had increased circulating lipid peroxides compared with normal pregnant women, as demonstrated by a 4.5‐fold higher concentration of plasma malondialdehyde (P<0.001). By using a NF‐κΒ luciferase reporter construct transfected into HUVEC, preeclamptic plasma was found to up‐regulate HUVEC NF‐κΒ activity by 2.5‐fold when compared with normal plasma (P<0.001). Inhibition of lipid peroxides with both vitamin E and N‐acetyl‐cysteine significantly reduced NF‐κΒ activation in response to preeclamptic‐plasma by 77% (P<0.005) and 76% (P<0.01), respectively. Flow cytometric analysis revealed that preeclamptic‐plasma also up‐regulated HUVEC ICAM‐1 expression by 30% (P<0.001) compared with normal‐plasma, while both vitamin E (P<0.005) and N‐acetyl‐cysteine (P<0.0001) significantly inhibited this effect. In summary, elevated plasma levels of lipid peroxides in preeclampsia are associated with increased NF‐κΒ activation and ICAM‐1 expression on HUVEC, which can be inhibited by vitamin E and N‐acetyl‐cysteine.