REDUCED RED BLOOD CELL DEFORMABILITY,AN INDICATOR FOR HIGH FETAL OR MATERNAL RISK,IS FOUND IN PREECLAMPSIA AND IUGR

Objective: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. Material and methods: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR (N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. Results: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. Conclusion: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae.     

HEAT SHOCK PROTEIN 70 IS NOT INCREASED IN WOMEN WITH SEVERE PREECLAMPSIA

Objective: The purpose of this study is to determine if heat shock protein 70 (Hsp 70), a marker of cellular stress, is elevated in pregnancies complicated by severe preeclampsia. Methods: Maternal blood was collected from women with severe preeclampsia (n=47) matched for delivery gestational age to normotensive pregnant controls (n=51). Hsp 70 concentrations were measured by standard ELISA techniques. Data were analyzed with the Student's t-test and chi-square test. Main outcome measures: The primary outcome measured was Hsp 70 concentrations. Our hypothesis prior to data collection was that HSP 70 would be increased in women with severe preeclampsia. Results: Compared with normotensive women, those with severe preeclampsia had similar maternal age, parity, delivery gestational age, maternal weight, and ethnicity. There was no difference in mean concentrations of Hsp 70 between women with severe preeclampsia and controls (35.4±96.7 vs. 30.1±11.5, p=0.80). Similar numbers of women with severe preeclampsia (n=28) and controls (n=30) had Hsp 70 concentrations below the 0.02 ng/dL level of detection (chi-square value=0.024, p=0.88). Conclusion: Hsp 70 concentrations are not elevated in women with severe preeclampsia.     

MATRIX METALLOPROTEINASE-2 IS ELEVATED IN THE PLASMA OF WOMEN WITH PREECLAMPSIA

Objective: We have recently demonstrated that matrix metalloproteinase-2 (MMP-2) alters vascular function through cleavage of vasoactive peptides, resulting in increased vasoconstriction and reduced vasodilation. We, therefore, hypothesized that MMP levels are increased in women with preeclampsia. In addition, because vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of preeclampsia and is involved in angiogenesis that requires the release of proteases to allow for migration of endothelial cells, we hypothesized that VEGF increases release of MMPs from endothelial cells.

Methods: We used zymographic analysis to evaluate MMP-2/MMP-9 levels in plasma of women with preeclampsia (n=12) compared to women with uncomplicated pregnancies (n=12). In addition, we evaluated the changes in the levels of MMP-2 and MMP-9 as well as tissue inhibitors of MMPs (TIMP-1 and TIMP-2) released by cultured human umbilical vein endothelial cells in response to VEGF (0.1–10 ng/mL).

Results: Our data showed that plasma MMP-2 levels were significantly higher in women with preeclampsia compared to women with uncomplicated pregnancies (arbitrary intensity units: 690 ±111 and 252 ±56, respectively, p<0.05). MMP-9 levels were below the level of detection. In addition, VEGF stimulated endothelial MMP-2 and MMP-9 release in a concentration- and time-dependent (6–24 h) manner. Moreover, VEGF stimulation of MMP release occurs without significantly affecting the release of TIMP-1 and TIMP-2.

Conclusions: These data suggest that VEGF promotes secretion of MMPs from endothelial cells that, in turn, could alter vascular function in women with preeclampsia.