Biomedical subjects

Louis L H Peeters

Publications and source records attributed to Louis L H Peeters.

15 recordsLinked to original sources

PubMed2006

PPAR gamma represses VEGF expression in human endometrial cells: implications for uterine angiogenesis.

UNLABELLED: Endometrial vasculature supports physiological uterine growth, embryonic implantation and endometrial pathology. Vascular endothelial growth factor (VEGF) is regulated by diverse developmental and hormonal signals, including eicosanoid ligands of PPARgamma. The action of natural and synthetic PPARgamma ligands on VEGF expression in primary and transformed human endometrial cell cultures was established by quantifying endogenous gene expression and transfected VEGF gene reporters. VEGF promoter-luciferase constructs were truncated and mutated to map functional sequences. Endometrial tissues and cells express PPARgamma protein. Treatment of transformed and primary endometrial cells with rosiglitazone, a synthetic PPARgamma agonist, or prostaglandin 15-deoxy-Delta12-14 J(2), a naturally occurring eicosanoid ligand, decreased VEGF protein secretion. In transiently transfected Ishikawa cells, rosiglitazone repressed VEGF gene promoter-luciferase activation with an IC(50) approximately approximately 50 nM. Truncated and mutated VEGF promoter constructs revealed that the PPARgamma-regulated domain is a direct repeat (DR)-1 motif -443 bp upstream of the transcriptional start site. CONCLUSIONS: PPARgamma ligands repress VEGF gene expression via a PPARgamma-responsive element (PPRE) in the VEGF gene promoter. Agonists of this nuclear receptor might be exploited pharmacologically to inhibit pathological vascularization in complications of pregnancy, endometriosis and endometrial adenocarcinoma.

Cell Line, Tumor↗

PubMed2006

Subclinical signs of vascular damage relate to enhanced platelet responsiveness among nonpregnant formerly preeclamptic women.

OBJECTIVE: In nonpregnant formerly preeclamptic women, the prevalence of occult cardiovascular abnormalities is increased. These high-risk women mildly benefit from low-dose aspirin in the prevention of recurrent disease. How this effect is mediated, either by affecting platelet or vascular function, is still unsettled. In this study, we tested the hypothesis that in these nonpregnant women, enhanced platelet responsiveness is common and related to microvascular damage. STUDY DESIGN: At least 6 months' postpartum we evaluated in 66 formerly preeclamptic women platelet count, volume, and in vitro response to low-dose ADP (0.5 microg/mL). Peripheral levels of fibronectin (microg/mL), von Willebrand factor antigen (%), C-reactive protein (high-sensitive CRP, mg/L), urinary albumin, and protein (24-hour collection, g/mol creatinine) served as markers of vascular damage. Hemodynamic function was determined by plasma volume (iodine I 125 HSA indicator dilution method, mL/kg lean body mass), cardiac index (Doppler, mL/min/m2), blood pressure and heart rate (Dinamap [Critikon, Tampa, FL], mm Hg and beats/min, respectively). Thereafter, we subdivided these 66 women into 2 subgroups either with (n = 10, 15%) or without increased platelet responsiveness (n = 56, 85%). Both groups were compared nonparametrically. RESULTS: Groups were comparable with respect to age, blood pressure, body mass index, parity, plasma volume, and cardiac index. Women with enhanced platelet responsiveness had higher levels of circulation fibronectin and CRP, and displayed more often albuminuria and proteinuria. In addition, even though platelet count was comparable between groups, the mean platelet volume was higher among women with enhanced platelet responsiveness. CONCLUSION: Fifteen percent of formerly preeclamptic women had enhanced platelet responsiveness, which was associated with elevated levels of various markers for (micro) vascular damage. We speculate that in these women platelets are presensitized on a relatively dysfunctional endothelium. Although this association does not prove causality, these results may indicate a subgroup of women who benefit from low-dose aspirin in the prevention of recurrent disease in a next pregnancy.

Adult↗

PubMed2006

Low plasma volume coincides with sympathetic hyperactivity and reduced baroreflex sensitivity in formerly preeclamptic patients.

BACKGROUND: Preeclampsia is associated with enhanced sympathetic activity as well as subnormal plasma volume. Meanwhile, in over 50% of these complicated pregnancies, the subnormal plasma volume has been found to persist for a prolonged period after pregnancy. The objective of this study is to test the hypothesis that in normotensive formerly-preeclamptic women, persistence of a subnormal plasma volume coincides with enhanced sympathetic activity and with it, an altered autonomic control of blood pressure. METHODS: Forty-eight formerly-preeclamptic women participated in this study. After measurement of their plasma volume by iodine 125-albumin indicator dilution, they were subdivided into a group with a normal plasma volume (plasma volume > 48 ml/kg lean body mass) and a group with a subnormal plasma volume (< or = 48 ml/kg lean body mass). We performed spectral analysis on their beat-to-beat blood pressure and heart rate recordings and compared both groups using non-parametric tests. RESULTS: Formerly-preeclamptic women with a subnormal plasma volume had a higher sympathetic activity (P = .001) and a lower baroreflex sensitivity (P = .04) than their counterparts with a normal plasma volume. CONCLUSION: In normotensive formerly-preeclamptic women, a subnormal plasma volume coincides with a higher sympathetic activity in the blood pressure regulation and lower baroreflex sensitivity. Whether these alterations in the autonomic control mechanisms are a cause or effect of the subnormal plasma volume remains to be elucidated.

Adult↗

PubMed2005

Vascular expression of adrenomedullin is increased in Wistar rats during early pregnancy.

OBJECTIVE: Circulating levels of adrenomedullin (ADM)--a vasodilator peptide with long-lasting effects--increase in the course of pregnancy. Neither the site nor the concomitant rate of ADM synthesis in pregnancy is known. The aim of this study was to test the hypothesis that the rise in plasma levels of ADM during pregnancy is paralleled by increased gene expression and protein levels in the vascular bed. STUDY DESIGN: We determined in cardiovascular and reproductive tissues of non-pregnant (n=10) and 10-days pregnant (n=10) Wistar rats ADM gene expression by semi-quantitative RT-PCR (normalized to GAPDH). As a support for the mRNA data, protein concentrations were measured by both ELISA and Western blot analysis. Finally, ADM in these tissues was localized by immunohistochemical staining. Statistical analysis was carried out by applying Mann-Whitney U-test. RESULTS: ADM mRNA levels in the abdominal aorta, renal artery and the kidney were increased during pregnancy. In addition, immunohistochemical staining in the kidney, uterus, abdominal aorta, renal, uterine and superior mesenteric artery was more intense as compared to non-pregnant rats. However, we observed lower concentrations of tissue ADM protein in pregnant rats, indicating an increased release of the hormone by the producing cells. CONCLUSION: Vascular ADM gene expression is increased in the first half of rat pregnancy. This coincides and may be functionally related to the institution of a high flow/low resistance circulation in pregnancy.

Adrenomedullin↗

PubMed2005

Vascular biology in implantation and placentation.

Pregnancy leads to dramatic changes of the vascular system of the mother and enables the development of a completely new vascular system within the growing embryo including the formation of the placenta as the exchange organ between both circulations. Besides a general adaptation of the maternal blood system, the uterine spiral arteries display the greatest changes. Within placental villi angiogenesis as well as vasculogenesis can be found already a few weeks after implantation. Both systems in parallel will determine the blood flow within the placental villi and the intervillous space. Finally, compromised blood flow on either side of the placental membrane will not only lead to fetal malnutrition, but will also trigger morphological changes of the villous trees. This review tries to cover all the above-mentioned topics and will try to depict the consequences of poor placentation on mother and fetus.

Animals↗

PubMed2005

Uterine artery remodeling in pseudopregnancy is comparable to that in early pregnancy.

During pregnancy, the lumenal diameter and wall mass of the uterine artery (UA) increase, most likely in response to the increased hemodynamic strain resulting from the chronically elevated uterine blood flow (UBF). In this remodeling process, the phenotype of vascular smooth-muscle cells (VSMC) is transiently altered to enable VSMC proliferation. These phenomena are already seen during early pregnancy, when the rise in UBF is still modest. This raises the question whether the newly instituted endocrine environment of pregnancy is involved in the onset of the pregnancy-related UA remodeling. We tested the hypothesis that the conceptus is not essential for the onset of UA remodeling of pregnancy. Six control and 18 pseudopregnant (Postcopulation Days 5, 11, and 17; n = 6 per subgroup) C57Bl/6 mice were killed and UAs were dissected and processed for either morphometric analysis or immunohistochemistry. The latter consisted of staining UA cross sections for the differentiation markers smooth muscle alpha-actin and smoothelin, and for the proliferation marker MKI67. We analyzed the UA changes in response to pseudopregnancy by ANOVA. Data are presented as mean +/- SD. By Day 11 of pseudopregnancy, the UA lumen was 25% wider and the media cross-sectional area 71% larger than in control mice. These differences were accompanied by reduced smoothelin expression and increased proliferation of UA medial VSMC. All UA morphological differences had returned or were in the process of returning to baseline values by Day 17 of pseudopregnancy. The structural and cellular aspects of UA remodeling as seen at midpregnancy are also seen in pseudopregnancy. These results support the concept that the conceptus does not contribute to the initiation of UA remodeling. We suggest that ovarian hormones trigger the onset of UA remodeling.

Actins↗

PubMed2005

Uterine artery remodeling and reproductive performance are impaired in endothelial nitric oxide synthase-deficient mice.

The progressive rise in uterine blood flow during pregnancy is accompanied by outward hypertrophic remodeling of the uterine artery (UA). This process involves changes of the arterial smooth muscle cells and extracellular matrix. Acute increases in blood flow stimulate endothelial production of nitric oxide (NO). It remains to be established whether endothelial NO synthase (eNOS) is involved in pregnancy-related arterial remodeling. We tested the hypothesis that absence of eNOS results in a reduced remodeling capacity of the UA during pregnancy leading to a decline in neonatal outcome. UA of nonpregnant and pregnant wild-type (Nos3+/+) and eNOS-deficient (Nos3-/-) mice were collected and processed for standard morphometrical analyses. In addition, cross sections of UA were processed for cytological (smoothelin, smooth muscle alpha-actin) and proliferation (Ki-67) immunostaining. We compared the pregnancy-related changes longitudinally and, together with the data on pregnancy outcome, transversally by analysis of variance with Bonferroni correction. During pregnancy, the increases in radius and medial cross sectional area of Nos3-/- UA was significantly less than those of Nos3+/+ UA. Smooth muscle cell dedifferentiation and proliferation were impaired in gravid Nos3-/- mice as deduced from the lack of change in the expression of smoothelin and smooth muscle alpha-actin, and the reduced Ki-67 expression. Until 17 days of gestation, litter size did not differ between both genotypes, but at birth the number of viable newborn pups and their weights were smaller in Nos3-/- than in Nos3+/+ mice. We conclude that absence of eNOS adversely affects UA remodeling in pregnancy, which may explain the impaired pregnancy outcome observed in these mice.

Adaptation, Physiological↗

PubMed2005

Maternal nonpregnant vascular function correlates with subsequent fetal growth.

OBJECTIVE: Evidence is accumulating that fetal growth is influenced by preexisting maternal disorder(s) hampering endothelial function. We tested the hypothesis that in nonpregnant normotensive, formerly preeclamptic women, vascular function predicts the development of fetal growth restriction. METHODS: In 60 formerly preeclamptic women, we measured central hemodynamic and vascular and clotting function mid follicular phase during the menstrual cycle. Inclusion for final analysis required besides normotension, a subsequent singleton pregnancy, established within 1 year after the prepregnant evaluation and ongoing beyond 16 weeks' gestation. In the ongoing pregnancy we determined birth weight and birth weight percentile. RESULTS: Among 60 formerly preeclamptic women, 45 (75%) were normotensive. Thirty-one (69%) participants succeeded in establishing an ongoing pregnancy within 1 year and were included for final analysis. Of the 31 subsequent pregnancies, 8 (26%) were complicated by fetal growth restriction. Prepregnant left and right uterine artery pulsatility index (PI) correlated inversely with carotid artery compliance ( r = 0.57, P = .005, r = 0.62, P = .002) and venous compliance ( r = 0.49, P = .02 and r = 0.45, P = .04, respectively). The latter, in turn, correlates with plasma volume ( r = 0.63, P = .001) and total peripheral vascular resistance index ( r = -0.45, P = .02). Finally, prepregnant left and right uterine artery PI correlated inversely with subsequent achieved fetal growth ( r = -0.68, P < .0001 and r = -0.58, P = .001, respectively). CONCLUSION: In nonpregnant normotensive, formerly preeclamptic women, an elevated uterine artery PI predisposes to subsequent restriction in fetal growth.

Adult↗

PubMed2005

Pre-pregnant prediction of recurrent preeclampsia in normotensive thrombophilic formerly preeclamptic women receiving prophylactic antithrombotic medication.

BACKGROUND: Both hemodynamic abnormalities and thrombophilia predispose to pregnancy-associated vascular complications such as fetal growth restriction, stillbirth, preeclampsia, and placental abruption. Antithrombotic treatment may reduce the risk for these events. In this study we tested the hypothesis that in normotensive thrombophilic formerly preeclamptic women certain alterations in hemodynamic function as measured under nonpregnant conditions predict the development of hypertensive disorders and/or fetal growth restriction in the subsequent pregnancy. METHODS: In 350 nondiabetic formerly preeclamptic women, we measured in the follicular phase of the menstrual cycle at least 5 months postpartum central hemodynamic, metabolic, and hemostatic variables. In the subsequent ongoing pregnancy we determined fetal outcome variables and the incidence of maternal vascular complications. In addition to a normotensive thrombophilic profile, inclusion for final analysis required a subsequent singleton pregnancy, established within 1 year following the pre-pregnant evaluation and ongoing beyond 16 weeks' gestation. As a consequence, 47 normotensive thrombophilic formerly preeclamptic women could be included for final analysis. All formerly preeclamptic participants received aspirin throughout pregnancy. Additionally, those with thrombophilia or hyperhomocysteinemia were treated with low molecular weight heparin and with pyridoxine and folic acid supplementation, respectively. RESULTS: Among 350 formerly preeclamptic women, 266 (76%) were normotensive and 84 (24%) hypertensive. About half (140/266) of normotensive formerly preeclamptic participants were thrombophilic. One hundred eighteen formerly preeclamptic participants succeeded in establishing an ongoing pregnancy within 1 year. From this subset of formerly preeclamptic women, 47 were normotensive thrombophilic; 23 remained normotensive (THROMB), whereas 24 developed at least gestational hypertension (COMPLITHROMB). Participants in the latter subgroup were more obese than those remaining normotensive. In addition, this former subset of women had a higher vascular resistance index, and a lower plasma volume and cardiac index. With respect to fetal outcome, COMPLITHROMB gave birth to an infant with a lower birth weight relative to THROMB. Preeclampsia with or without the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome recurred in 26% of the participants in the whole thrombophilic group, in which a low pre-pregnant plasma volume and a raised vascular resistance predisposed for recurrent hypertensive disorders. CONCLUSION: Pre-pregnant hemodynamic, metabolic, and clotting variables in formerly preeclamptic women can predict hypertension in the subsequent pregnancy.

Adult↗

PubMed2004

Aging blunts remodeling of the uterine artery during murine pregnancy.

OBJECTIVE: The progressive increase in uterine blood flow (UBF) during pregnancy is accommodated by morphologic changes in the uterine artery (UA) in a process defined as arterial remodeling. This process is accompanied by changes in cytoskeletal architecture of the arterial smooth muscle cells (SMCs) and surrounding extracellular matrix (ECM). Aging reduces flow-induced arterial remodeling. We studied changes in the murine UA during pregnancy and on the effects of aging on the capacity of the UA to remodel in response to pregnancy. METHODS: We determined morphologic and cytologic changes in UA from nonpregnant and pregnant mice aged 12 weeks (young) and 40 weeks (old) and correlated them with their reproductive performance. RESULTS: In young mice, pregnancy induced an early increase in UA wall mass, which preceded lumen widening. These changes were not accompanied by altered densities of elastin and collagen in the ECM of the medial layer. Smooth muscle cell proliferation increased in midpregnancy and was paralleled by a transient decrease in smoothelin and smooth muscle alpha-actin expression. In old mice, these pregnancy-dependent changes in the UA wall were either absent or markedly reduced. Although by day 11 of pregnancy litter size did not differ between both age groups, the number of viable pups in old mice by day 17 of pregnancy and at birth was 25% and 60% less than in young mice. CONCLUSION: Outward hypertrophic remodeling of the UA during pregnancy in young mice is characterized by transient phenotypic modulation and proliferation of SMCs and alterations in the composition of the ECM. In contrast, in older mice, UA remodeling is markedly reduced and accompanied with a loss of viable fetuses near term pregnancy.

Aging↗

PubMed2004

Angiotensin II sensitivity in nonpregnant formerly preeclamptic women and healthy parous controls.

BACKGROUND: In women prone to develop hypertensive complications, vascular reactivity fails to decrease in early pregnancy. Since hypertensive syndromes of pregnancy seem to be superimposed on a preexisting disorder, we tested the hypothesis that in formerly preeclamptic women, as compared to healthy parous controls, circulatory reactivity to angiotensin II is enhanced in the follicular phase of the menstrual cycle. METHODS: Sixty formerly preeclamptic women were subdivided into a hypertensive (HYPERT, n = 14), a normotensive thrombophilic (THROMB, n = 26), and a normotensive nonthrombophilic (ASYMPT, n = 20) subgroup. In these women and in 11 healthy parous controls we assessed at least 5 months postpartum at day 5 (+/-2) of the menstrual cycle the following variables: body weight, height, plasma volume, reactivity to infused angiotensin II of arterial blood pressure, heart rate, glomerular filtration rate (GFR), effective renal blood flow, and the hormones of the renin-angiotensin-aldosterone (RAAS) axis. RESULTS: At baseline, THROMB did not differ from controls. In contrast, ASYMPT exhibited slight overweight, reduced plasma volume, and reduced renal blood flow. HYPERT much resembled ASYMPT except for the overweight, renal perfusion, and GFR. Infusion of angiotensin II led to comparable decreases in renal perfusion and filtration, and to increases in blood pressure. However, sensitivity to this substance correlated inversely with relative and absolute sizes of the plasma volume compartment. CONCLUSION: Circulatory sensitivity to infused angiotensin II is comparable between nonpregnant formerly preeclamptic women and healthy parous controls. However, responsiveness to this agent is enhanced among women with a contracted plasma volume compartment, a condition commonly observed among formerly preeclamptic women.

Adult↗

PubMed2004

Fetal cardiovascular response to large placental chorioangiomas.

A large placental chorioangioma is a relatively rare condition, which in 50% of all cases will lead to maternal and fetal complications. Since chorioangiomas are often associated with significant arterio-venous shunting within the placenta, several fetal hemodynamic compensatory mechanisms are initiated. Ultrasound and color Doppler flow mapping are important for the prenatal diagnosis of chorioangiomas, as an early prenatal diagnosis is crucial to minimize the risks for fetal well-being. Close surveillance of pregnancy and pregnancy termination by cesarean section at the earliest signs of fetal cardiac decompensation are indicated to reduce fetal and neonatal complications. Novel intrauterine treatment options include intravascular transfusion, fetoscopic devascularization, microcoil embolization, and intravascular injection of absolute alcohol.

Female↗

PubMed2003

Low plasma volume following pregnancy complicated by pre-eclampsia predisposes for hypertensive disease in a next pregnancy.

OBJECTIVE: A large number of women with a history of pre-eclampsia/HELLP have a low plasma volume at least six months postpartum. The objective of this study was to determine whether a low plasma volume in formerly pre-eclamptic women and HELLP patients is associated with an increased risk for recurrent hypertensive complications in a next pregnancy. DESIGN: Prospective observational study. SETTING: Tertiary obstetric centre. SAMPLE: Formerly pre-eclamptic women and controls. METHODS: In 316 women with a history of pre-eclampsia and/or HELLP, we measured, plasma volume along with haemodynamic, metabolic and haemostatic variables at least six months postpartum. A group of 22 healthy parous controls was used as a reference. After standardising plasma volume for body mass index, women were subdivided into normotensive and normal plasma volume (n = 199), normotensive and low plasma volume (n = 76) and hypertensive (n = 41) subgroups, which were compared for demography, clinical parameters and course of a next pregnancy. MAIN OUTCOME MEASURES: Recurrent hypertensive disease of pregnancy. RESULTS: Relative to the normal plasma volume subgroup, normotensive women in the low plasma volume subgroup have a higher body mass index, a lower total vascular compliance and a shorter estimated systemic circulation time. They have a higher HOMA index and higher fasting triglyceride levels. In normotensive and hypertensive former patients alike, low plasma volume is associated with a higher recurrence of hypertensive complications in a next pregnancy compared with normotensive women with normal plasma volume. CONCLUSION: Low plasma volume in normotensive women with a history of pre-eclampsia and/or HELLP is associated with overweight, reduced vascular compliance and insulin resistance and a predisposition for recurrent pre-eclampsia and HELLP syndrome in a next pregnancy.

Adult↗

PubMed2001

Hemodynamic changes in pseudopregnancy in chronically instrumented, conscious rats are preserved after hysterectomy.

Hemodynamic changes in early-pregnant and pseudopregnant rats are comparable, indicating that the trophoblast does not contribute to these changes. It is unclear whether the presence of the uterus is needed for the normal early-pregnancy hemodynamic adaptation. In this study we tested the hypothesis that uterine factors do not contribute to the systemic hemodynamic changes in early pseudopregnancy. To this end, we studied systemic hemodynamics in conscious pseudopregnant rats subjected to a hysterectomy, and compared these results with those obtained in a control group of pseudopregnant rats. The animals were studied on days 4, 8, 12 and 19 postmating. On day 8 of pseudopregnancy, cardiac output has increased by 23+/-7% in the hysterectomized group and 15+/-5% in the control group. In both groups this rise in cardiac output was entirely accomplished by a rise in stroke volume, by 28+/-8% and 19+/-5%, respectively. Mean arterial pressure did not change appreciably. Therefore, total peripheral resistance also decreased in both groups (17+/-6%) by day 8. After day 12 the hemodynamic parameters returned to baseline. We conclude that systemic hemodynamic changes in hysterectomized pseudopregnant rats closely resemble those in intact pseudopregnant rats. Therefore, the uterus does not seem to play a role in these changes. This supports the hypothesis that only hormones from ovarian origin trigger the initial hemodynamic adaptation to early pregnancy.

Animals↗

PubMedDate not supplied

Posttraumatic stress disorder after pre-eclampsia: an exploratory study.

Information about the psychological sequelae of pre-eclampsia (PE) is scarce. Post-traumatic stress disorder (PTSD) may develop after exposure to a stress condition. This study explored whether PE predisposes to PTSD in patients and their partners. Primiparas with a recent history of preterm PE (n=18), preterm birth (PT; n=29), term PE (n=23), or uneventful term birth (C; n=43), and most of their partners completed questionnaires measuring PTSD, depression and related psychological factors. About one-fourth of patients developed PTSD after preterm PE as well as after PT. It occurred in 17% after term PE and in none of the control subjects. A substantial minority of partners was also affected. PTSD symptoms were strongly related to individual psychological characteristics (peritraumatic dissociation, negative interpretations of symptoms, and thought suppression) rather than to objective indicators of condition-severity. The data suggest that PE predisposes to PTSD, primarily but not exclusively resulting from concomitant preterm birth.

Adult↗