Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition

Bowen, Robin S.; Zhang, Yanping; Gu, Yang; Lewis, David F.; Wang, Yuping

doi:10.1016/j.placenta.2004.07.007

Cited by 52 publications

(36 citation statements)

References 26 publications

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“…Recently, we and others found that trophoblast cells from preeclamptic placentas released more soluble phospholipase A2 than cells from normal placentas (11,21) and increased trophoblast phospholipase A2 activity is positively correlated to the higher levels of TX produced by trophoblasts from preeclamptic placentas. Under an oxidative stress condition, both phospholipase A2 activity and TX production are increased in trophoblasts from preeclampsia (11). It is believed that the activation of phospholipase A2 -AA pathway favors the TX synthesis in placental trophoblasts.…”

Section: Discussionmentioning

confidence: 75%

“…In fact, elevated maternal levels of soluble phospholipase A2 and AA have been reported in women with preeclampsia (19,20). Recently, we and others found that trophoblast cells from preeclamptic placentas released more soluble phospholipase A2 than cells from normal placentas (11,21) and increased trophoblast phospholipase A2 activity is positively correlated to the higher levels of TX produced by trophoblasts from preeclamptic placentas. Under an oxidative stress condition, both phospholipase A2 activity and TX production are increased in trophoblasts from preeclampsia (11).…”

Section: Discussionmentioning

confidence: 79%

“…We tested our hypotheses: 1) disproportionate releases of TX and PGI2 towards apical and basal directions by placental trophoblasts; and 2) increased basal release of TX by trophoblasts from preeclamptic placentas. Because our previous study suggests that increased TX production by trophoblast cells from preeclamptic placentas may result from an increase in PLA 2 release that leads to an activation of arachidonic acid (AA) -cyclooxygenase pathway (11), in this study we further examined effects of apical exposure of AA on trophoblast releases of TX and PGI2 in the presence or absence of aspirin, a cyclooxygenase inhibitor, in our chamber cultures.…”

Section: Introductionmentioning

confidence: 99%

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Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Zhao

Lewis

et al. 2008

Placenta

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Objective-To investigate apical and basal releases of thromboxane (TX) and prostacyclin (PGI2) by trophoblasts (TCs) from normal and preeclamptic (PE) placentas.Methods-TCs isolated from normal and PE placentas were incubated in cell culture inserts for 48hrs. Medium from the upper (apical) and the lower (basal) chambers were then collected separately and measured for TX and PGI2 by their stable metabolites of TXB2 and 6-keto PGF1α by ELISA. Apical and basal releases of TX and PGI were also examined with apical exposure of TCs to arachidonic acid (AA)+/-aspirin at different concentrations. Villous tissue expressions for PGI synthase, TX synthase and TX (TP) receptor were examined by immunohistochemistry.Results-1) TXB2, but not 6-keto PGF1α, concentrations were significantly higher in the lower than in the upper chambers with both normal and PE TCs (p<0.01); 2) apical exposure of TCs to AA resulted in a significant increase in TX releases towards both the upper and the lower chambers in normal TCs (p<0.01), but only a significant increase in the upper chamber in PE TCs (p < 0.01); 3) aspirin could attenuate AA-induced TX release both in the upper and the lower chambers in normal, but not in PE, TCs (p<0.01), respectively; 4) there were no differences in 6-keto PGF1α productions both in normal and PE TCs treated with AA +/− aspirin; 5) intense staining of TX synthase and TP receptor was seen in syncytiotrophoblast layer, villous core vessels and stromal cells in preeclamptic placental tissue sections.Conclusion-Predominant basal release of TX together with intense staining of TX synthase and TP receptor in trophoblasts, stromal cells and villous core vessels are found in placentas from PE. We speculate if predominant basal release of TX by TCs occurs in vivo as we found in our in vitro culture condition, basal released TX may play a significant role in increased placental vasoconstriction such as in PE.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Zhao

Lewis

et al. 2008

Placenta

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“…The placenta produces ANG II [12][13][14][15][16], TX [17,18] and ET [19][20][21]. To study which vasoactivators and their pathways produced by PE placenta were more responsible for regulating the vasomotor response in the placental vasculature, selected receptor antagonists or inhibitors of three major vasoconstrictors, ANG II, TX and ET-1, were used.…”

Section: Discussionmentioning

confidence: 99%

“…Past studies have described that placental tissues produce ANG II [12][13][14][15][16], TX [17,18] and ET [19][20][21] and they are major contributors to the vasoconstriction in PE. Receptors for ANG II [2,6,[22][23][24][25], TX [26,27], and ET [28] are present in placental trophoblasts and vasculature.…”

Section: Introductionmentioning

confidence: 99%

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

2007

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Inadequate blood flow and increased vasoconstriction of the placenta contribute to pregnancy associated disorders such as preeclampsia (PE). Because placental vessels lack autonomic innervation, humoral effects of the placenta must play critical roles in regulation of fetal-placental vascular contractility. In this study, we examined the nature of humoral factors produced by PE trophoblasts on placental vessel contractility using an organ bath perfusion model. Vasomotor responses were studied in vitro using placental chorionic plate arteries. Vessel rings from third branch chorionic plate arteries were dissected from human placentas following normal or PE delivery. The arterial rings were equilibrated in Krebs Henseleit buffer and exposed to placental conditioned medium, which was prepared by culture of villous tissue from PE placentas. Receptor antagonists for angiotensin II (ANG II), thromboxane (TX), and endothelin (ET) were used to determine which humoral factor produced by placental tissue (trophoblasts) was more effective in promoting vasoconstriction. The role of angiotensin converting enzyme (ACE) and non-ACE ANG II generating enzymes in regulation of placental vasomotor tone were also investigated. A total of 80 arterial rings from 48 placentas were studied. Our results showed: 1) enhanced vasomotor tone in arteries from PE placentas compared to those from normal placentas; 2) PE-CM induced vaso-constrictive activity could be partially attenuated by receptor antagonists for TX, ANG II and ET, respectively; and 3) chymostatin (a chymase inhibitor) produced a stronger inhibitory effect than captopril (ACE inhibitor) on PE conditioned medium induced vasoconstriction. Our data demonstrate increased vasocontractility in PE placentas and suggest that the non-ACE pathway is probably a major source of ANG II produced in the human placenta.

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Pathophysiology of Preeclampsia and L-Arginine/L-Citrulline Supplementation as a Potential Strategy to Improve Birth Outcomes

Ortiz

Mosso

Alcudia

et al. 2023

Advances in Experimental Medicine and Biology

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Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition

Cited by 52 publications

References 26 publications

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

Pathophysiology of Preeclampsia and L-Arginine/L-Citrulline Supplementation as a Potential Strategy to Improve Birth Outcomes

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