The Pathophysiology of Endothelial Function in Pregnancy and the Usefulness of Endothelial Markers

Abstract

Aim. The aim of this study was to assess coagulation markers of endothelial damage and examine new markers of endothelial activation such as matrix metalloproteinases (MMPs) in a group of healthy pregnant women. Matrix metalloproteinase (MMP)-2, in particular, plays a major role in the degradation of the extracellular matrix confirming its essential function in both the survival (angiogenesis) and death of endothelial cells.Detection of specific coagulation factors, mainly released from the vascular endothelium such as vWF, sTM (soluble thrombomodulin) and ePCR (endothelial protein C receptor) and factors dependent on endothelial activation such as t-PA and PAI-1, could provide information on possible endothelial dysfunction and help differentiate pregnant patients with an altered thrombotic state.Methods. Healthy pregnant women underwent complete assessment for endothelial damage (as vWF, vWF activity, sTM, ePCR, EMP, MMP-2, MMP-9 and TIMP-2) using the ELISA and other methods.Results and Conclusions. The results show that endothelial activation during pregnancy is different from that in other pathological conditions involving endothelial damage and typically characterized by higher levels of both coagulation endothelial markers and MMPs. In pregnancy, changes in extracellular matrix composition and matrix metalloproteinase activity also occur and promote vascular remodeling but, only in the uterus. Predisposing risk factors for epithelial dysfunction, and vascular mediators associated with vascular remodeling must be assessed from concentrations in whole blood. The levels of MMPs are not increased in the circulation and the local situation in the uterus cannot be monitored this way.However, MMP-2 processes and modulates the functions of many other vasoactive and pro-inflammatory molecules including adrenomedullin, big endothelin-1, calcitonin gene-related peptide, CCL7/MCP-3, CXCL12/SDF-1, galectin-3, IGFBP-3, IL-1 Beta, S100A8, and S100A9. These molecules represent new potential molecular markers of endothelial damage during pregnancy.

Early identification of women with HELLP syndrome who need plasma exchange after delivery

“…When plasma exchange is used in the treatment of other diseases (mainly thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome), the main goals are removal of some plasma components such as antibodies, immune complexes, and endogenous and exogenous toxins, and replacement of some plasma proteins and coagulation factors [8,[17][18][19][20][21]. The mechanism of PPEX in HELLP patients is unknown and controversial, but it might involve removal of aggregating and procoagulant factors released from both activated platelets and endothelial cells because HELLP is associated with severe endothelial dysfunction [8,22]. Reports suggest that PPEX in HELLP can be stopped earlier than is done in thrombotic thrombocytopenic purpura because in the former, the cause (pregnancy) is no longer present.…”

Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse

“…16,32–35 For example, matrix metalloproteinase-2 (MMP2), which has been shown to modulate CCL-7, is upregulated late in pregnancy by high levels of estrogen and progesterone. 36 Therefore the increase in Ccl7 and Cxcl12 expression in KO mice could be due to differences in tissue remodeling between the two genotypes due to Loxl1 deficiency.…”

“…1 Hormonal changes during pregnancy affect physiological parameters such as maternal circulation as well as tissue biomechanics and composition of the uterus and vagina, 39 some of which are mediated via MMPs, which contribute to ECM remodeling. 36,40 One limitation of this work is that we focused on multiple time points after delivery and only one reproducible time point during pregnancy. Therefore, we may have missed variations in cytokine expression during gestation.…”

Сучасні Підходи До Лікування Ускладнень Вагітності Після Застосування Дрт.

“…Перебіг вагітностей, що наступили в результаті лікування безпліддя методами ДРТ, характеризується високою частотою ускладнень, зокрема загрозою переривання вагітності (75 %), передчасними пологами (ЗО %), невиношуванням (45 %), плацентарною дисфункцією (60 %) [1][2][3][4][5]. Незважаючи на існуючі методи лікування і профілактики ускладнень вагітності, недостатня увага приділяється етіопатогенетичним чинникам розвитку гестаційних ускладнень після ДРТ, зокрема імунологічним факторам та проблемам ангіогенезу [6][7][8][9][10]. Тому пошук нових методів лікування і профілактики, направлених на зменшення ускладнень вагітності після ДРТ, залишається актуальним у сучасному акушерстві [11].…”