Maternal Vascular System Research Articles

Piezo1 channels mediate vasorelaxation of uterine arteries from pseudopregnant rats.

Introduction: There is a great increase in uterine arterial blood flow during normal pregnancy, which is a result of the cardiovascular changes that occur in pregnancy to adapt the maternal vascular system to meet the increased metabolic needs of both the mother and the fetus. The cardiovascular changes include an increase in cardiac output and more importantly, dilation of the maternal uterine arteries. However, the exact mechanism for the vasodilation is not fully known. Piezo1 mechanosensitive channels are highly expressed in endothelial and vascular smooth muscle cells of small-diameter arteries and play a role in structural remodeling. In this study, we hypothesize that the mechanosensitive Piezo1 channel plays a role in the dilation of the uterine artery (UA) during pregnancy. Methods: For this, 14-week-old pseudopregnant and virgin Sprague Dawley rats were used. In isolated segments of UA and mesenteric resistance arteries (MRA) mounted in a wire myograph, we investigated the effects of chemical activation of Piezo1, using Yoda 1. The mechanism of Yoda 1 induced relaxation was assessed by incubating the vessels with either vehicle or some inhibitors or in the presence of a potassium-free physiological salt solution (K+-free PSS). Results: Our results show that concentration-dependent relaxation responses to Yoda 1 are greater in the UA of the pseudo-pregnant rats than in those from the virgin rats while no differences between groups were observed in the MRAs. In both vascular beds, either in virgin or in pseudopregnant, relaxation to Yoda 1 was at least in part nitric oxide dependent. Discussion: Piezo1 channel mediates nitric oxide dependent relaxation, and this channel seems to contribute to the greater dilation that occurs in the uterine arteries of pseudo-pregnant rats.

Gestational Thrombophilia

The woman's body undergoes several physiological changes during the gestational period. Risk factors and comorbidities can cause pathophysiological changes in this period, especially in the maternal vascular system, triggering thrombophilia. This clotting disorder increases the thrombus formation risk, especially in the uteroplacental circulation. The study aimed to conduct a thorough review of the main approaches to diagnosis and treatment in reducing patient morbidity and mortality. This is an integrative review with qualitative data searched in Pubmed, BVS and Cochrane Library. A total of 624 studies were found, 591 were excluded outside the inclusion criteria, and 33 were selected. According to the careful search, thrombophilias can be hereditary or acquired, the former when there is a predisposition to venous occlusion and the latter from other clinical conditions. Pregnancy is a pro-thrombotic event and increases the chances of thrombus occurrence, triggering a series of pregnancy complications, such as intrauterine death, early or late miscarriage, and premature birth. However, if diagnosed early, there is a favorable prognosis for the woman and the fetus. To reduce these impacts of gestational thrombophilia, it is imperative to train primary health care and private clinics professionals to promote and treat health and basic diagnostic tests on pregnant women. Thus, performing early intervention avoiding the development of maternal-fetal complications.

Downregulation of Ribosomal Contents and Kinase Activities Is Associated with the Inhibitive Effect on the Growth of Group B Streptococcus Induced by Placental Extracellular Vesicles.

Simple SummaryThe bioactive properties of extracellular vesicles (EVs) in the physiological and pathophysiological conditions of pregnancy and cancers have been well investigated. However, the interaction of EVs and bacterial cells has not been studied yet. Transferring and releasing of cargos in EVs intracellularly impact the function of target cells. In this study, we investigated the effect of placental EVs on the growth of opportunistic pathogens such as Group B Streptococcus (GBS), which is a major cause of some complications of pregnancy. We found that placental micro-EVs or nano-EVs attenuated the growth of a Gram-positive bacterium, GBS. This attenuative effect at least partially required an interaction of placental EVs with GBS. Proteomic analysis showed that changes in protein synthesis or cellular energy in GBS may contribute to this inhibitory effect.Background: Like many other cell types, the human placenta produces large amounts of extracellular vesicles (EVs). Increasing evidence has shown that placental EVs contribute to the regulation of maternal immune and vascular systems during pregnancy via the transfer of their cargos. In this study, we investigated the effect of placental EVs on the growth of opportunistic pathogens that commonly colonise the female reproductive tract. Methods: Gram-positive bacterium Group B Streptococcus (GBS) and Gram-negative bacterium Escherichia coli (E. coli) were treated with placental EVs that were collected from placental explant cultures, and the growth, susceptibility, and resistance to antibiotics of the bacteria were measured. In addition, comparative proteomics analysis was also performed for the GBS with or without exposure to placental EVs. Results: When treated with placental micro-EVs or nano-EVs, the GBS growth curve entered the stationary phase earlier, compared to untreated GBS. Treatment with placental EVs also inhibited the growth of GBS on solid medium, compared to untreated GBS. However, these biological activities were not seen in E. coli. This attenuative effect required interaction of placental EVs with GBS but not phagocytosis. In addition, the susceptibility or resistance to antibiotics of GBS or E. coli was not directly affected by treatment with placental EVs. The proteomic and Western blotting analysis of GBS that had been treated with placental EVs suggested that the downregulation of cellular components and proteins associated with phosphorylation and cell energy in GBS may contribute to these attenuative effects. Conclusion: We demonstrated the attenuative effect of the growth of GBS treated with placental EVs. Downregulation of cellular components and proteins associated with phosphorylation and cell energy may contribute to the physiological changes in GBS treated with placental EVs.

Preeclampsia Status Controls Interleukin-6 and Soluble IL-6 Receptor Release from Neutrophils and Endothelial Cells: Relevance to Increased Inflammatory Responses.

Increased neutrophil–endothelial binding and inflammatory responses are significant pathophysiological events in the maternal vascular system in preeclampsia, a hypertensive disorder in human pregnancy. Interleukin 6 (IL-6) and its soluble receptors (soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)) are critical inflammatory mediators. During pregnancy, maternal IL-6 and sgp130 levels were increased, but sIL-6R levels were decreased, in women with preeclampsia compared to normotensive pregnant women. However, little is known about differences in IL-6, sIL-6R, and sgp130 production by neutrophils and endothelial cells between normal pregnancy and preeclampsia. To study this, we isolated neutrophils and cultured human umbilical vein endothelial cells (HUVECs) from normal and preeclamptic pregnancies. Production of IL-6, sIL-6R, and sgp130 was measured. The role of placental factor(s)-mediated neutrophil production of IL-6, sIL-6R, and sgp130 was also determined by pretreating neutrophils with placental conditioned medium generated from placental villous cultures. We found that IL-6 and sgp130 were mainly produced by endothelial cells, while sIL-6R was mainly produced by neutrophils. Endothelial cells from preeclampsia produced significantly more IL-6 and sgp130, and neutrophils from preeclampsia produced significantly less sIL-6R than normal pregnancy cells. Interestingly, production of IL-6, sIL-6R, and sgp130 were time-dependently increased when neutrophils and endothelial cells were co-cultured. We also found that neutrophils from normal pregnancies produced more IL-6, but less sIL-6R, after being primed by preeclamptic-placental conditioned medium. These results demonstrated that neutrophils and endothelial cells have different capacities in producing IL-6, sIL-6R, and sgp130 between normal pregnancy and preeclampsia. These results also provide evidence that the placenta plays a role in inducing neutrophil activation in preeclampsia.

The Emerging Role of the Prokineticins and Homeobox Genes in the Vascularization of the Placenta: Physiological and Pathological Aspects.

Vasculogenesis and angiogenesis are key processes of placental development, which occur throughout pregnancy. Placental vasculogenesis occurs during the first trimester of pregnancy culminating in the formation of hemangioblasts from intra-villous stem cells. Placental angiogenesis occurs subsequently, forming new blood vessels from existing ones. Angiogenesis also takes place at the fetomaternal interface, allowing essential spiral arteriole remodeling to establish the fetomaternal circulation. Vasculogenesis and angiogenesis in animal models and in humans have been studied in a wide variety of in vitro, physiological and pathological conditions, with a focus on the pro- and anti-angiogenic factors that control these processes. Recent studies revealed roles for new families of proteins, including direct participants such as the prokineticin family, and regulators of these processes such as the homeobox genes. This review summarizes recent advances in understanding the molecular mechanisms of actions of these families of proteins. Over the past decade, evidence suggests increased production of placental anti-angiogenic factors, as well as angiogenic factors are associated with fetal growth restriction (FGR) and preeclampsia (PE): the most threatening pathologies of human pregnancy with systemic vascular dysfunction. This review also reports novel clinical strategies targeting members of these family of proteins to treat PE and its consequent effects on the maternal vascular system.

COVID-19 in pregnancy: possible mechanisms not to be discounted

SARS-CoV-2 has infected more than 16 million people worldwide. Related complications and death from COVID-19 disease and their underlying pathophysiology are intensely investigated. Pregnant women are among the affected. Although the severity of disease in pregnancy does not appear to be increased, the effects of infection on pregnancy should not escape careful examination. The currently known receptor for the virus, ACE2, regulates the renin-angiotensin system and is increased during pregnancy. Virus–receptor interactions may have significant effects on placental function, fetal development, and maternal immunity. The manifestation of cardiovascular complications of infection produces the hypothesis that a significant effect of the virus may be its influence on the maternal vascular system. Interference with the vascular adaptations to pregnancy and the post-partum may have implications for concurrent and future pregnancies as well as for long-term cardiovascular health. We should not miss the opportunity to learn from this virus about the physiology of pregnancy.

New Insights Into the Role of Placental Aquaporins and the Pathogenesis of Preeclampsia.

Accumulated evidence suggests that an abnormal placentation and an altered expression of a variety of trophoblast transporters are associated to preeclampsia. In this regard, an abnormal expression of AQP3 and AQP9 was reported in these placentas. Recent data suggests that placental AQPs are not only water channel proteins and that may participate in relevant processes required for a normal placental development, such as cell migration and apoptosis. Recently we reported that a normal expression of AQP3 is required for the migration of extravillous trophoblast (EVT) cells. Thus, alterations in this protein might lead to an insufficient transformation of the maternal spiral arteries resulting in fluctuations of oxygen tension, a potent stimulus for oxidative damage and trophoblast apoptosis. In this context, the increase of oxygen and nitrogen reactive species could nitrate AQP9, producing the accumulation of a non-functional protein affecting the survival of the villous trophoblast (VT). This may trigger the exacerbated release of apoptotic VT fragments into maternal circulation producing the systemic endothelial dysfunction underlying the maternal syndrome. Therefore, our hypothesis is that the alteration in the expression of placental AQPs observed at the end of gestation may take place during the trophoblast stem cell differentiation, disturbing both EVT and VT cells development, or during the VT differentiation and turnover. In both situations, VT is affected and at last the maternal vascular system is activated leading to the clinical manifestations of preeclampsia.

Aberrant pro-atrial natriuretic peptide/corin/natriuretic peptide receptor signaling is present in maternal vascular endothelium in preeclampsia.

Corin is a serine protease that converts pro-atrial natriuretic peptide (pro-ANP) to atrial natriuretic peptide (ANP), a cardiac hormone that regulates salt-water balance and blood pressure. ANP is degraded by natriuretic peptide receptor (NPR). This study was to determine if aberrant pro-ANP/corin/NPR signaling is present in maternal vascular system in preeclampsia. Maternal venous blood was obtained from 197 pregnant women (84 normotensive, 16 complicated with chronic hypertension (CHT), 11 mild and 86 severe preeclampsia). Plasma corin and pro-ANP concentrations were measured by enzyme-linked immunosorbent assay. Maternal subcutaneous fat tissue was obtained from 12 pregnant women with cesarean section delivery (6 normotensive and 6 preeclampsia). Vascular ANP and its receptors NPR-A, NPR-B, and NPR-C expression were examined by immunostaining of paraffin embedded subcutaneous fat tissue sections. Corin concentrations were significantly higher in mild (2.78 ± 0.67 ng/ml, p < .05) and severe (2.53 ± 0.18 ng/ml, p < .01) preeclampsia than in normotensive (1.58 ± 0.08 ng/ml) and CHT (1.55 ± 0.20 ng/ml) groups. Pro-ANP concentrations were significantly higher in CHT (1.59 ± 0.53 ng/ml, p < .05) and severe preeclampsia (1.42 ± 0.24 ng/ml, p < .01) than in normotensive (0.48 ± 0.06 ng/ml) and mild preeclampsia (0.52 ± 0.09 ng/ml) groups. ANP and NPR-B expression was undetectable in maternal vessels from normotensive and preeclamptic pregnancies, but reduced NPR-A expression and increased NPR-C expression was found in maternal vessel endothelium in preeclampsia. ANP is a vasodilator and NPR-C is a clearance receptor for ANP. The finding of upregulation of NPR-C expression suggests that circulating ANP clearance or degradation is increased in preeclampsia. These results also suggest that pro-ANP/corin/NPR signaling is dominant in the vascular system in preeclampsia.

Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries

Pregnancy is a physiologically stressful condition that generates a series of functional adaptations by the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia, affect the function of the maternal and offspring vascular systems, after delivery and into adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. These alterations in later life range from fertility problems to alterations in the central nervous system or immune system, among others. It is important to note that rates of morbi-mortality due to pregnancy complications including preeclampsia, as well as cardiovascular diseases, have a higher incidence in Latin-American countries than in more developed countries. Nonetheless, there is a lack both in the amount and impact of research conducted in Latin America. An impact, although smaller, can be seen when research in vascular disorders related to problems during pregnancy is analyzed. Therefore, in this review, information about preeclampsia and endothelial dysfunction generated from research groups based in Latin-American countries will be highlighted. We relate the need, as present in many other countries in the world, for increased effective regional and international collaboration to generate new data specific to our region on this topic.

Células progenitoras endoteliales en el embarazo normal y la preeclampsia

El embarazo es un reto para el sistema cardiovascular materno, necesitando de adaptación sistémica y marcados cambios locales en el útero. La adaptación cardiovascular materna al embarazo involucra una respuesta fisiológica compleja a la presencia de un feto en crecimiento, incluyendo alteraciones de las células endoteliales vasculares que contribuyen a la marcada disminución de la resistencia vascular sistémica. El descubrimiento de las células progenitoras endoteliales ha generado un considerable interés en el campo de la biología vascular. Estas células pueden ser movilizadas hacia la circulación por factores de crecimiento y pueden apoyar la salud del endotelio vascular por varios mecanismos. Estas células se originan de una población de células mononucleares circulantes y tienen la capacidad de formar nuevos vasos y contribuyen a la reparación vascular. Patologías del embarazo, como la preeclampsia, incrementan el riesgo de complicaciones y están asociadas con disfunción endotelial.

STA54. Preeclampsia – Myths are still stronger than scientific data

Introduction During pregnancy close interactions between the maternal and fetal system exist with the placenta as the organ situated between the two individuals. In cases where this crosstalk is disturbed, preeclampsia may develop. During the last decades a number of hypotheses have been developed to describe the etiology of this syndrome. However, so far all of them have failed. Objectives One of the current hypotheses – although wrong as well – is still strongly supported by the scientific community although it has become clear in recent years that a variety of arguments that are needed to support this hypothesis are not valid at all. Methods This list comprises the following arguments, known to be wrong today: (1) Failure in trophoblast invasion is a prerequisite for preeclampsia. (2) Placental hypoxia is present in cases suffering from preeclampsia. (3) During preeclampsia, the placenta is the main source for angiogenic factors in maternal blood. Additionally, another important issue needs attention: (4) The quality of a biomarker only depends on its concentration in maternal blood. Results These four arguments and issues will be discussed. It will become clear that (1) changes in trophoblast invasion are not related to preeclampsia; (2) placental hypoxia does not exist at all in cases with preeclampsia; (3) the maternal vascular system is the main source for angiogenic factors; and (4) pre-analytics are increasingly important to maintain the quality of samples to test for biomarkers. Conclusion Due to the availability of new data it is more than needed to update the hypotheses on the etiology of preeclampsia. It is quite detrimental to keep with old but no longer valid hypotheses and hindering the rise of newer and better hypotheses. Therefore, the above mentioned arguments including trophoblast invasion, placental hypoxia and the source of angiogenic factors need to be taken into account when further discussing the etiology of preeclampsia.

Placental extracellular vesicles and feto-maternal communication.

The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental extracellular vesicles and the known effects of such vesicles on maternal cells/systems, especially those of the maternal immune and vascular systems.

Maternal–fetal interactions, predictive markers for preeclampsia, and programming

During pregnancy close interactions between the maternal system and the fetal system via the placenta exist that result in a powerful crosstalk between both individuals. Looking for predictive biomarkers in maternal blood is extremely difficult because of this crosstalk as such markers may be derived from only maternal sources, only placental sources or both. In particular, the concentrations of markers derived from both sources may vary because of the huge variety of reasons and sources. During the last decade this has misled a number of scientists and clinicians who tried to decipher the sources of markers and the impact of the placenta and/or the maternal vascular system. A few examples for predictive biomarkers are presented, the placenta-specific marker placental protein 13 (PP13) and the angiogenic marker PlGF being released from both mother and placenta. Finally, a further reason why biomarkers may not be successful in predicting all cases of preeclampsia is that different causative routes lead to the development of preeclampsia. The differences in the development of preeclampsia not only explain why markers may or may not have a predictive value, but also why some mothers and/or children may display long-term effects later in life.

Absence of meristems in androgenic embryos of Datura metel (L.) induces secondary embryogenesis in vitro

The induction of secondary embryos in androgenic and zygotic embryos of Datura metel (L.) (Solanaceae) was investigated by excising their shoot and root meristems and culturing the hypocotyls on Nitsch medium. Androgenic embryos produced secondary embryos on the hypocotyl. Histological sections showed secondary embryo development was independent of maternal tissue with no connection to the maternal vascular system. The zygotic embryos produced shoot buds and adventitious roots from the cut surface. Shoot buds had vascular connections with the maternal tissue. Excision of both meristems produced more secondary embryos than excision of the apical meristem alone. Excision of apical meristems in embryogenically competent immature embryos and their in vitro culture could potentially produce secondary embryos on the hypocotyls. The significance of these results is the clonal multiplication of the primary embryo at an early stage of embryo development. The meristem excision steps are easily performed under sterile conditions.

Vascular effects of maternal alcohol consumption

Maternal alcohol consumption during pregnancy is a significant field of scientific exploration primarily because of its negative effects on the developing fetus, which is specifically defined as fetal alcohol spectrum disorders. Though the effects on the mother are less explored compared with those on the fetus, alcohol produces multiple effects on the maternal vascular system. Alcohol has major effects on systemic hemodynamic variables, endocrine axes, and paracrine factors regulating vascular resistance, as well as vascular reactivity. Alcohol is also reported to have significant effects on the reproductive vasculature including alterations in blood flow, vessel remodeling, and angiogenesis. Data presented in this review will illustrate the importance of the maternal vasculature in the pathogenesis of fetal alcohol spectrum disorders and that more studies are warranted in this field.

Microchimérisme fœtal : soi et non soi, finalement qui sommes-nous ?

For a long time, the conventional view was that the fetus and maternal vascular system are kept separate. In fact there is a two-way traffic of immune cells through the placenta and the transplacental passage of cells is in fact the norm. The fetal cells can persist in a wide range of woman's tissue following a pregnancy or an abortion and she becomes a chimera. Fetal cells have been found in the maternal circulation and they were shown to persist for almost three decades in humans, thus demonstrating long-term engraftment and survival capabilities. Microchimerism is a subject of much interest for a number of reasons. Studies of fetal microchimerism during pregnancy may offer explanations for complications of pregnancy, such as preeclampsia, as well as insights into the pathogenesis of autoimmune disease which usually ameliorates during pregnancy. The impact that the persistence of allogenic cells of fetal origin and the maternal immunological response to them has on the mother's health and whether it is detrimental or beneficial to the mother is still not clear. Although microchimerism has been implicated in some autoimmune diseases, fetal microchimerism is common in healthy individuals. On the beneficial side, it has been proposed that genetically disparate fetal microchimerism provides protection against some cancers, that fetal microchimerism can afford the mother new alleles of protection to some diseases she has not, that fetal microchimerism can enlarge the immunological repertoire of the mother improving her defense against aggressor. Fetal cells are often present at sites of maternal injury and may have an active role in the repair of maternal tissues.

Foetal and neonatal energy metabolism in pigs and humans: a review

The aim of this review was to elaborate a conceptual framework of the most important aspects of the main biochemical processes of synthesis and breakdown of energy substrates that human and pig foetuses and newborns can use during the transition from foetus to newborn. Under normal physiological conditions, the growth and development of the foetus depends upon nutrients such as glucose, lipids and amino acids. In addition to the maternal and foetal status, genetic factors are also reported to play a role. The main function of the placenta in all species is to promote the selective transport of nutrients and waste products between mother and foetus. This transport is facilitated by the close proximity of the maternal and foetal vascular systems in the placenta. The foetus depends on the placental supply of nutrients, which regulates energy reserves by means of glycogen storage. Also, the synthesis of foetal hepatic glycogen guarantees energy reserves during perinatal asphyxia or maternal hypoglycaemia. However, the foetus can also obtain energy from other resources, such as gluconeogenesis from the intermediary metabolism of the Krebs cycle and most amino acids. Later, when the placental glucose contribution ends during the transition to the postnatal period, the maturation of biological systems and essential metabolic adaptations for survival and growth is required. The maintenance of normoglycaemia depends on the conditions that determine nutrient status throughout life: the adequacy of glycogen stores, the maturation of the glycogenolytic and gluconeogenic pathway, and an integrated endocrine response.

Elevated Maternal Soluble Gp130 and IL-6 Levels and Reduced Gp130 and SOCS-3 Expressions in Women Complicated With Preeclampsia

Increased inflammatory response plays a significant role in the vascular pathophysiology in preeclampsia. However, the mechanism for increased inflammatory response in preeclampsia is largely unknown. Interleukin (IL)-6 levels are elevated in women with preeclampsia. IL-6 and its receptors, IL-6R and glycoprotein (gp)130, play a critical role in mediating antiinflammatory response via induction of SOCS-3 (suppressor of cytokine signaling-3). However, IL-6 receptor levels and expressions have not been studied in preeclampsia. In this study, we measured IL-6 and its 2 soluble receptors, soluble IL-6R and soluble gp130, in maternal plasma from normal and preeclamptic pregnant women and found that not only IL-6 but also soluble gp130 levels were significantly higher in preeclamptic women than in normotensive pregnant controls. We further examined IL-6R, gp130, and SOCS-3 expressions in maternal vessels and leukocytes and found that gp130 and SOCS-3 expressions were downregulated in both vessel endothelium and leukocytes from preeclampsia. Different patterns for IL-6R and gp130 expressions were found. IL-6R expression was also downregulated in leukocytes from preeclampsia. Our results suggest that increased plasma soluble gp130/soluble IL-6R/IL-6 ratio and reduced membrane transsignaling gp130 expression could contribute to decreased SOCS-3 expression and subsequent reduction in SOCS-3 antiinflammatory activity in women with preeclampsia. Thus, reduced gp130 and SOCS-3 expressions may offer, at least in part, a plausible explanation of reduced antiinflammatory protection in the maternal vascular system in preeclampsia.

Influence of the vascular endothelial growth factor on the development of severe pre-eclampsia or HELLP syndrome

The aim of this study was to compare the maternal serum concentrations of the vascular endothelial growth factor (VEGF) in patients whose pregnancies were complicated by pre-eclampsia or HELLP syndrome with those of healthy pregnant controls and to study its relationship with the hormonal and nutritive function of the placenta. The study group consisted of 30 primaparae who suffered from either severe pre-eclampsia (n = 16) or from HELLP syndrome (n = 14). 30 healthy pregnant woman of the same gestational age served as control group. Maternal serum VEGF concentrations were determined by using a commercially available Sandwich immunoassay (Quantikine(®), R&D Systeme, Wiesbaden, Germany). Estradiol, estriol and progesterone serum levels were measured by performing a radioimmunoassay (Biermann, Bad Nauheim, Germany). The mean serum VEGF concentration of the study group (172.0 ± 98.9 pg/ml) was significantly increased, compared with the mean serum VEGF concentration of the control group (41.4 ± 30.5 pg/ml) (U test: P < 0.001). In the subgroup of the study patients with HELLP syndrome, significantly lower VEGF levels were measured than in patients suffering from severe pre-eclampsia (109.2 ± 68.5 pg/ml vs. 219.0 ± 72.9. U test: P < 0.05). In all study and control patients, a significantly positive correlation between serum estradiol and VEGF concentration could be found (Spearman's rank correlation: P < 0.05). An increased placental expression due to local hypoxia and an increased extraplacental production, e.g., in endothelial cells of the fetal or maternal vascular system, in macrophages or in smooth muscle cells, could be discussed as causes for the raised serum VEGF concentration in patients suffering from severe pre-eclampsia or HELLP syndrome.

Evaluation of adrenomedullin and endothelin-1: Are they factors in the adaptation of maternal vascular system in normotensive pregnancy

The aim of our study was to analyse the role of adrenomedullin (AM) and endothelin-1 (ET-1) in the adaptation of the maternal vascular system in normotensive pregnancy. Twenty-eight pregnant women, who were normotensive throughout the duration of their pregnancy, were recruited into the study. Plasma levels of AM and ET-1 at each trimester were measured and the AM/ET-1 ratio was calculated. Our experiment showed a significant decrease in plasma concentrations of AM in the first trimester for the study group (n=28) compared with the non-pregnant control group (n=16). There was also a significant decrease in plasma concentrations of ET-1 in all three trimesters (P<0.05) and a significant increase in the AM/ET-1 ratio in all three trimesters (P<0.05) for the study group compared with the control group. An alteration in vascular equilibrium between AM and ET-1, favouring AM, may be a reason why the physiological adaptation of the maternal vascular system to pregnancy occurs during normotensive pregnancy.