Plasma Hemopexin Activity in Pregnancy and Preeclampsia

Abstract

Enhanced hemopexin activity may be associated with normal pregnancy, but not with preeclampsia. Decreased hemopexin in pre-eclamptic patients may be due to enhanced plasma ATP, which is possibly promoted by diminished activity of vascular ecto-apyrase.

Danger Signals From ATP and Adenosine in Pregnancy and Preeclampsia

“…5,20 This is for instance seen in diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and preeclampsia. 6,21,22 To avoid ATP-induced pathological effects, cells can hydrolyze ATP into ADP and AMP by the enzymes ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and alkaline phosphatase.…”

“…11 These enzymes are expressed in many tissues, including the placenta, and their activity and expression are changed in preeclampsia (Table S1 in the online-only Data Supplement). 6,11 Adenosine generally counteracts ATP-induced effects. 5,23 The final inflammatory effect of ATP depends on the balance between ATP and adenosine ( Figure 1).…”

“…5,6 ATP is released by hypoxic and necrotic tissue, for instance by the hypoxic placenta. 7,8 Release into the circulation causes activation of immune and endothelial cells, 5,9 which in turn can also produce ATP, resulting in a cascade of activation.…”

Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by α1-microglobulin

“…In fact, a haptoglobin polymorphism has been associated with essential hypertension, which is predisposing for developing PE [14]. Free heme is primarily scavenged by hemopexin, but this activity is reduced in PE [15]. The haptoglobin-Hb and hemopexin-heme complexes are cleared from the circulation by the two receptor-mediated pathways CD163 and CD91, and subsequently degraded in lysosomes [16].…”

An alternative view of the proposed alternative activities of hemopexin

“…84 Recently, this group also reported that the plasma of pregnant (but not pre-eclamptic) women produces reduced staining of glomerular ectoapyrase 82,85 and that the plasma of some renal transplant recipients has increased protease activity. 84 However, attributing these plasma activities to hemopexin or, moreover, solely to a modification of hemopexin without more direct evidence remains presumptive.…”