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(Hypertension. 2009;53:270.)
© 2009 American Heart Association, Inc.

Original Articles

Increased Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Expression in the Maternal Vasculature of Women With Preeclampsia

Role for Peroxynitrite

From the Departments of Obstetrics and Gynaecology (S.S., Y.X., S.T.D.) and Physiology (S.S., Y.X., S.T.D.) and Cardiovascular Research Group and Women and Children’s Health Research Institute (S.T.D.), University of Alberta, Edmonton, Alberta, Canada; and Vascular Physiology (T.S.), National Cardiovascular Center Research Institute, Osaka, Japan.

Correspondence to Sandra T. Davidge, Departments of Ob/Gyn and Physiology, 232 HMRC, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. E-mail sandra.davidge{at}ualberta.ca

Preeclampsia is a hypertensive disorder unique to pregnancy, in which the placenta may release factors into the maternal circulation resulting in systemic effects. Small dense low-density lipoprotein (LDL; which is susceptible for oxidation) is increased in preeclampsia. Lectin-like oxidized LDL receptor-1 (LOX-1) is a receptor for oxidized LDL. However, the expression levels and the regulation of LOX-1 in the maternal vasculature of women with preeclampsia are unknown. We hypothesized that there is an increased LOX-1 expression in arteries from women with preeclampsia. We further hypothesized that circulating factors in the plasma of women with preeclampsia would upregulate the LOX-1 expression in vascular endothelial cells and contribute to vascular endothelial oxidative stress. We observed abundant LOX-1 expression and the presence of oxidized LDL in arteries from women with preeclampsia, which was negligible in arteries from normotensive pregnant women. Human umbilical vein endothelial cells treated for 24 hours with 2% plasma from preeclamptic women increased LOX-1 expression and oxidized LDL uptake, as well as induced oxidative stress, as evidenced by increased NADPH oxidase activity and superoxide and peroxynitrite levels. These effects were significantly reduced by pretreatment with blocking antibody or small interfering RNA to LOX-1, as well as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III), chloride (FeTPPS), a peroxynitrite scavenger. Exogenous peroxynitrite and 3-morpholino sydnonimine (SIN-1) increased LOX-1 protein and mRNA expression. In conclusion, increased LOX-1 expression in the systemic vasculature of preeclampsia women provides a fundamental insight into the pathology of preeclampsia and likely contributes to the induction and maintenance of vascular oxidative stress.

Key Words: preeclampsia • LOX-1 • NADPH oxidase • endothelium • peroxynitrite

This article has been cited by other articles:

				S. Sankaralingam, H. Xu, Y. Jiang, T. Sawamura, and S. T. Davidge Evidence for Increased Methylglyoxal in the Vasculature of Women With Preeclampsia: Role in Upregulation of LOX-1 and Arginase Hypertension, October 1, 2009; 54(4): 897 - 904. [Abstract] [Full Text] [PDF]

				S. Sankaralingam, H. Xu, and S. T. Davidge Arginase contributes to endothelial cell oxidative stress in response to plasma from women with preeclampsia Cardiovasc Res, September 3, 2009; (2009) cvp277v2. [Abstract] [Full Text] [PDF]