Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function

Abstract

Objective To investigate the hypothesis that, should there be an increase in deported syncytiotrophoblast microvillous membrane fragments in pre-eclampsia, it may cause maternal vascular endothelial dysfunction.Design Syncytiotrophoblast microvillous membrane (STBM) vesicles, prepared from normal term placentae, were perfused through small subcutaneous arteries isolated from fat biopsies obtained at caesarean section. Endothelial function of these arteries was studied by determining acetylcholineinduced relaxation after preconstriction with noradrenaline. As controls, physiological buffer or red blood cell membranes in physiological buffer were used and endothelial function similarly estimated. Transmission electron microscopy was performed on arteries after perfusion.Sample STBM vesicles, isolated from the placentae of three healthy women undergoing elective caesarean section for reasons unrelated to pre-eclampsia, were suspended in physiological buffer. Subcutaneous fat arteries were obtained from a separate group of 13 normotensive pregnant women, also undergoing elective caesarean section at term.Results Perfusion with red blood cell membranes or physiological buffer had no significant effect on the concentration dependent relaxation in arteries preconstricted with noradrenaline. However, after 2 h perfusion with STBM vesicles, arteries showed a significant reduction in relaxation to acetylcholine, indicative of altered endothelial function. Transmission electron microscopy of arteries perfused with STBM vesicles confirmed endothelial disruption.Conclusions STBM vesicle perfusion specifically altered the relaxation response of preconstricted maternal subcutaneous fat arteries to acetylcholine, suggesting an alteration in endothelial dependent relaxation. Deported microvilli may therefore be capable of producing endothelial cell damage and endothelial dysfimction observed in the maternal syndrome of pre-eclampsia.

Hypertension in pregnancy

“…Furthermore, vesicles prepared from STBM reduced the relaxation response of preconstricted subcutaneous fat arteries from normotensive pregnant women to acetylcholine, presumably due to decreased endothelial dependent relaxation. 164 Thus some of the endothelial dysfunction seen in PE might be secondary to the consequences of increased trophoblast invasion.…”

“…162 The local generation of nitric oxide (NO) may also be involved; there is increased NO activity in the veins of the dorsum of the hand in pregnancy. 163 Blood flow itself is a major regulator of endothelial NO synthesis, and Cockell et al (1997) 164 have shown in small arteries from fat biopsies in healthy pregnant women that NO responses to flow are enhanced by comparison with those from non-pregnant subjects. Furthermore, the forearm vascular response to NO synthase inhibition is enhanced in normal pregnancy by comparison with non-pregnant women, also suggesting a rô le for NO in the vasodilatation of pregnancy.…”

Difference in serum nephrin expression between normal and preeclamptic pregnancies: A preliminary study

“…Bit Na Rae Kim, et al Serum nephrin expression in preeclampsia 위자 체계 등이 관여하는데, 이 과정에서 중요한 역할을 하는 것이 혈 관 형성인자들이다 [7][8][9]. 태반 형성과정에 이상이 생기면 태반에 허 혈이 생기고 그에 따라 전신적으로 세포독성물질들이 분비되어 모체 의 혈관 내피에 손상을 주게 된다 [12].…”

“…태반 형성과정에 이상이 생기면 태반에 허 혈이 생기고 그에 따라 전신적으로 세포독성물질들이 분비되어 모체 의 혈관 내피에 손상을 주게 된다 [12]. 또한 최근 연구들에 따르면 전 자간증에서 혈관 형성인자들의 조절에 이상 소견이 보이는 것이 밝혀 졌다 [1,9,[13][14][15][16][17][18][19][20]. 그 대표적인 혈관 형성인자들이 placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF) 등이다.…”

“…PlGF, VEGF 등은 임신기간 동안 증가하게 되어 혈관 형성과 혈관 이완물질들의 형성에 작용하게 되는데, 전자간증에서는 PlGF는 감소하고 VEGF는 양적으로는 증가를 보이나 생물학적 활성은 오히려 감소하는 것으로 밝혀졌다 [21,22]. 또 한 순환하는 혈관형성 억제인자인 sFlt-1은 증가하게 된다 [9,14,20,23]. sFlt-1은 VEGF의 soluble receptor로 VEGF에 결합하여 중화시키는 작 용을 한다.…”