Differential expression of lactate dehydrogenase isozymes (LDH) in human placenta with high expression of LDH-A(4) isozyme in the endothelial cells of pre-eclampsia villi

Abstract

To evaluate the role of LDH isozymes in the human placenta during the third trimester, placentae were obtained from patients with normal pregnancy and pre-eclampsia. LDH-A(4)isozyme was immunolocalized primarily in the fetal endothelial cells while LDH-B(4)isozyme was predominantly present in syncytiotrophoblasts. This distinct cellular expression pattern of LDH isozymes was confirmed in HUVE and JEG cells. In addition to demonstrating the presence of five LDH isozymes in the placenta, zymograms showed that there was predominant activity of LDH-A(4)isozyme in HUVE cells and high activity of LDH-B(4)in JEG cells. Quantitative studies of LDH by agarose gel electrophoresis and Northern analysis in patients concluded that LDH-A(4)isozyme was increased in pre-eclampsia. The LDH-A(4)isozyme activity increased (P< 0.01) approx 1.6-fold in pre-eclampsia but there was no difference in the LDH-B(4)isozyme activity between placentae from normal compared to pre-eclampsia pregnancy. The level of LDH-A mRNA was increased (P< 0.05) approx twofold in pre-eclampsia. We conclude that the LDH-A gene in the endothelial cells of the placenta within the fetal microvasculature is increased in pre-eclampsia, probably as a result of hypoxia. LDH-A(4)isozyme activity and gene expression in placental endothelial cells, therefore, is a marker for the endothelial pathology seen in pre-eclampsia.