Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 48, Issue 2, Pages 284-291Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.10.052
Keywords
Hemoglobin; Oxidative stress; Oxidation markers; ROS; alpha(1)-Microglobulin; Preeclampsia; Free radicals
Funding
- Swedish Research Council [7144, 5775, 14251]
- ALF
- Swedish Society for Medical Research
- Royal Physiographic Society in Lund
- Foundations of Greta and Johan Kock and Alfred Osterlund
- Swedish Foundation for International Cooperation in Research and Higher Education
- Blood and Defence Network
- Lund University
- Crafoord Foundation
- Thelma Zoega Foundation
- Preelumina AB
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Preeclampsia is a major cause of morbidity and mortality during pregnancy. To date, the pathogenesis of the disease is not fully understood. Recent studies show that preeclampsia is associated with overexpression of the hemoglobin genes alpha 2 and gamma and accumulation of the protein in the vascular lumen of the placenta. Hypothesizing that cell-free hemoglobin leaks from the placenta into the maternal circulation and contributes to the endothelial damage and symptoms by inducing oxidative stress, we analyzed fetal and adult hemoglobin (HbF, HbA), haptoglobin, oxidation markers, and the heme scavenger and antioxidant alpha(1)-microglobulin in plasma, urine, and placenta in preeclamptic women (n = 28) and women with normal pregnancy (n = 27). The mean plasma concentrations of HbF, HbA, protein carbonyl groups, membrane peroxidation capacity, and alpha(1)-microglobulin were significantly increased in preeclamptic women. The levels of total plasma Hb correlated strongly with the systolic blood pressure. The plasma haptoglobin concentrations of women with preeclampsia were significantly depressed. Increased amounts of alpha(1)-microglobulin mRNA and protein were found in placenta from preeclamptic women, and the levels of plasma and placenta alpha(1)-microglobulin correlated with the plasma Hb concentrations. The heme-degrading form t-alpha(1)-microglobulin was significantly increased in urine in preeclampsia. These results support the idea that hemoglobin-induced oxidative stress is a pathogenic factor in preeclampsia. (C) 2009 Published by Elsevier Inc.
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