Preeclampsia – Studies on the Placenta and B-type Natriuretic Peptide

Abstract: Preeclampsia has several pathophysiological pathways, but the placenta has a central role. The pathophysiology appears to differ between the two subtypes – early- and late-onset preeclampsia. In clinically evident preeclampsia, maternal circulatory levels of the cardiac peptide B-type natriuretic peptide (BNP) and its cleavage fragment NT-proBNP are elevated, but whether or not the peptides are involved in the pathophysiology of preeclampsia is unknown. The overall aim of the current work was to expand knowledge of preeclampsia pathophysiology, with a main focus on the relationship between BNP and NT-proBNP, and early- and late-onset preeclampsia.In Paper I, the placental transcriptional profiles of early- and late-onset preeclampsia were compared by using microarrays and bioinformatics. A total of 196 transcripts were differently regulated in the two groups. Using qRT-PCR, mRNA levels of the two angiogenesis-related transcripts ACVRL1 and EGFL7 were confirmed to be lower in early-onset preeclampsia than in both late-onset preeclampsia and early controls.In Paper II, the circulatory levels of NT-proBNP were higher in both early- and late-onset preeclampsia than in gestational age-matched controls. BNP mRNA and protein were detected by qRT-PCR and immunohistochemistry in placentas from both women with preeclampsia and controls.In Paper III, circulatory levels of NT-proBNP were measured in the early second-trimester in women who later developed early-onset preeclampsia and in women who continued to have normal pregnancies. No differences were found between the two groups of women.In Paper IV, the secretion of NT-proBNP, and the mRNA levels of BNP and BNP receptors were investigated in cultured primary trophoblasts. Low levels of NT-proBNP were found in the supernatants of term but not first-trimester trophoblasts. BNP and BNP-receptor mRNA were detected in term trophoblasts.The results of this work strengthen the concept of the two subtypes of preeclampsia (early- and late-onset) having partly different pathophysiological pathways. The results also indicate that the placenta releases BNP and that BNP may have receptor-mediated effects on the placenta.