Adrenomedullin, a New Vasoactive Peptide, Is Increased in Preeclampsia

Abstract

Abstract-Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (PϽ0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252Ϯ29 versus 112Ϯ10 fmol/mol creatinine) and umbilical vein plasma (18.1Ϯ2.1 versus 8.5Ϯ1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level. (Hypertension. 1998;32:758-763.)

Shared biomarkers between female diastolic heart failure and pre‐eclampsia: a systematic review and meta‐analysis

“…However, because these worked with inconvertible measurement units, two separate meta‐analyses with inconsistent results were carried out. The first showed lower ADM in pre‐eclampsia; mean difference −5.60 pmol/L; 95%CI −14.76–3.55; P  = 0.23 88, 91, 94. The second meta‐analysis showed higher ADM in pre‐eclampsia; mean difference 41.44 pg/mL; 95%CI 12.58–70.31; P  = 0.005 89, 90.…”

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

“…16 Immunostaining data have shown either normal or decreased placental ADM expression. 19,20 ADM also has demonstrable effects as a cytokine growth factor, being able to inhibit or stimulate cancer cell proliferation, depending on the cell type and culture conditions, 1 and hence, might influence placental function by paracrine mechanisms.…”

Adrenomedullin in mammalian embryogenesis

“…Other studies did not find variations in AM immunoreactivity or between both groups (Di Iorio et al, 1998c); (3) finally, with regard to umbilical vein blood and amniotic fluid, AM levels were reported to be significantly increased in preeclamptic pregnant women (Di Iorio et al, 1997b), which suggests that increased AM concentrations might be necessary to maintain placental vascular resistance at a physiological level.…”

“…Within human placenta at term, AM is localized primarily in extravillous trophoblast cells and in the syncytiotrophoblast, but is also present in endothelial cells of villous blood vessels and in maternal decidual cells (Di Iorio et al, 1998c;Kanenishi et al, 2000Kanenishi et al, , 2001Macri et al, 1998;Marinoni et al, 1998). Occasionally, immunocytochemical staining for AM has also been reported in cytotrophoblast cells and in the mesenchyma and inflammatory cells within the villi (Kanenishi et al, 2001;Macri et al, 1998).…”

“…Some controversy, however, has arisen from discordances in data of different groups studying AM implication as a pathophysiogical substance in preeclampsia (Di Iorio et al, 1998a): (1) some groups have not found a significant difference in maternal plasma AM concentration between preeclamptic and normotensive pregnant women (Di Iorio et al, 1998c;Jerat et al, 2001;Makino et al, 1999c;Minegishi et al, 1999), whereas others have reported a significant maternal plasma decrease in patients with preeclampsia as compared to normal pregnancies (Hata et al, 1997); (2) concerning AM immunoreactivity in fetoplacental structures from pregnancies with preclampsia, AM staining has either been found to be significantly decreased (specifically in villous syncytiotrophoblasts) with respect to normotensive pregnancies (Kanenishi et al, 2000), or to be increased in the fetal membranes and umbilical artery (Makino et al, 1999c) as compared to controls. Other studies did not find variations in AM immunoreactivity or between both groups (Di Iorio et al, 1998c); (3) finally, with regard to umbilical vein blood and amniotic fluid, AM levels were reported to be significantly increased in preeclamptic pregnant women (Di Iorio et al, 1997b), which suggests that increased AM concentrations might be necessary to maintain placental vascular resistance at a physiological level.…”