RAGE-dependent cellular activation is known to cause inflammatory and oxidative damage in various cells via NF-κB transactivation. A truncated form of RAGE (sRAGE) has been shown to bind RAGE ligands, thereby preventing downstream RAGE signaling. This study was conducted to identify changes in systemic sRAGE levels in normal pregnancy as well as in pathological states of excess oxidative stress such as pre-eclampsia.
In a nested case-control study, we analyzed serum specimens obtained throughout pregnancy, but before labor, from 57 healthy pregnant women (CRL), and 34 severe preeclamptic women (sPE). Serum samples from 11 non-pregnant reproductive age women were used to identify the effect of pregnancy on sRAGE. sRAGE levels were measured by sensitive immunoassay.
1) Pregnancy is associated with a significant decrease in serum sRAGE as compared to the non-pregnant state (p=0.007); 2) The analysis of the healthy pregnant CRL group demonstrates that the serum sRAGE system is not gestational age regulated (r= −0.117, p=0.387); 3) Compared with gestational age matched CRL specimens, preeclamptic women had significantly higher serum sRAGE concentrations reaching levels 2-fold higher between 24-33 weeks of gestation (median [IQR] sPE: 671 [482-1477] vs CRL: 367 [310-479] pg/mL, p<0.001).
Lower levels of sRAGE in pregnancy compared to the non-pregnant state may render pregnant women vulnerable to obstetrical pathogenic processes associated with oxidative stress and inflammation. An elevation in serum concentrations of sRAGE observed in sPE may reflect the existence of a protective mechanism against oxidative stress.
© 2007 Mosby, Inc. Published by Elsevier Inc. All rights reserved.