Endothelial Angiotensin II Generation Induced by Placenta-derived Factors From Preeclampsia

Abstract

Hypersensitivity to angiotensin II contributes to the increased vasoconstriction in preeclampsia. In this study, we determined whether placenta-derived factors could affect endothelial cell angiotensin II generation. Our results showed that more angiotensin II was produced by endothelial cells treated with preeclampsia placental conditioned medium than the cells treated with normal conditioned medium or untreated controls. To determine which pathway, angiotensin-converting enzyme or nonangiotensin-converting enzyme angiotensin-generating enzyme/chymase, might be involved in preeclampsia conditioned medium induced angiotensin II generation, angiotensin-converting enzyme inhibitor captopril and chymotrypsin inhibitors were applied to the cell culture either separately or in combination. We found that chymotrypsin inhibitor, but not captopril, could attenuate the increased angiotensin II generation. To further test specific effects of the protease on endothelial cell angiotensin II generation, endothelial cells were grown in cell culture inserts and chymotrypsin was added to the upper chamber of the cell culture (apical exposure). The medium in the lower chamber (basal direction) was collected and measured for angiotensin II. Our results showed that apical exposure of endothelial cells to the protease resulted in a concentration-dependent increase in basal release of angiotensin II. Angiotensin II receptor-1 expression was also upregulated in cells treated with preeclampsia conditioned medium or chymotrypsin. This data suggest that placenta-derived factors may activate chymase-angiotensin pathway in endothelial cells. Moreover, increased endothelial cell basal release of angiotensin II in response to the protease stimulation further suggests that angiotensin II levels in the circulation may not necessarily reflect angiotensin II generation within the vascular wall.

The role of angiogenic, anti-angiogenic and vasoactive factors in pre-eclamptic African women : early- versus late-onset pre-eclampsia

“…This may imply that there is no quantitative increase in vasopressors, but rather an increase in sensitivity to the existing quantity of vasoactive factors present in pre-eclamptic women. Our study provides proof of this by showing elevated expression of the AT1 receptors in late-onset pre-eclamptic patients compared to the normotensive controls, chronic hypertensive and early-onset pre-eclamptic groups, thereby accounting for the heightened sensitivity to the powerful vasoconstrictor angiotensin II, which is in accordance with previous studies 52,53…”

The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: Roles in trophoblast invasion and angiogenesis?

“…Alternatively, Ang I may be converted to Ang II through the action of chymase, by an ACE independent pathway [21]. Chymase is expressed in the human placenta, its activity is increased in placentae from women with preeclampsia [22], and it may increase Ang II production [23].…”

Relationships among adiponectin gene polymorphisms, proteinuria and increased blood pressure in the context of placental diseases

“…In the clinic, the patients may show a series of manifestations, such as high blood pressure and proteinuria. 23,24 As a vasoactive substance reacting with its specific receptors (AdipoR1 and AdipoR2), adiponectin has important physiological roles, such as protecting vascular endothelial cells, increasing insulin sensitivity, inhibiting inflammation and inhibiting atherosclerosis. By measuring plasma adiponectin in 1842 pregnant women in early pregnancy and tracking the outcomes of their pregnancies, D'Anna et al 4 found that plasma adiponectin in patients with preeclampsia was lower than in pregnancy-induced hypertension patients and normal patients.…”