Maternal Angiotensin-converting Enzyme Research Articles

Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

The Gene Variants of Maternal/Fetal Renin-Angiotensin System in Preeclampsia: A Hybrid Case-Parent/Mother-Control Study

Preeclampsia (PE) is a common pregnancy-related complication, and polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) are believed to contribute to PE development. We implemented a hybrid study to investigate the influence of maternal and fetal ACE I/D, ACE G2350A, AGT M235T, AGT T174M, and AT1R A1166C polymorphisms on PE in Han Chinese women. Polymorphisms were genotyped in 1,488 subjects (256 patients experiencing PE, along with their fetuses and partners, and 360 normotensive controls with their fetuses). Transmission disequilibrium tests revealed that ACE I/D (P = 0.041), ACE G2350A (P = 0.035), and AT1R A1166C (P = 0.018) were associated with maternal PE. The log-linear analyses revealed that mothers whose offspring carried the MM genotype of AGT M235T had a higher risk of PE (OR = 1.54, P = 0.010), whereas mothers whose offspring carried the II genotype of ACE I/D or the GG genotype of ACE G2350A had a reduced risk (OR = 0.58, P = 0.039; OR = 0.47, P = 0.045, respectively). Our findings demonstrate that fetal ACE I/D, ACE G2350A, AGT M235T, and AT1R A1166C polymorphisms may play significant roles in PE development among pregnant Han Chinese women.

Fetopathies associated with exposure to angiotensin converting enzyme inhibitor from Tropaeolum majus L.

The prevalence of the use of herbal medicines is on the rise across the world, especially amongst pregnant women. A fact that draws attention is that many species commonly used by pregnant women, including the Tropaeolum majus L. (Tropaeolaceae), also present inhibitory activity on the angiotensin-converting enzyme (ACE). Herein, we have investigated the effects of T. majus extract (HETM) on fetal development, evaluating its relationship with possible ACE inhibitory activity. Pregnant Wistar rats were treated with different HETM doses (3, 30 and 300 mg/kg/day) from gestational days 8–20. Rats were sacrificed on the day 20 of pregnancy and the following parameters were evaluated: clinical symptoms of maternal toxicity; maternal body weight; feed and water intake; maternal liver, kidney, and ovary weights, maternal ACE activity and aldosterone levels, live fetuses mean; dead fetuses percentage, fetus weight, and fetal malformation. All pregnant rats treated with high HETM doses showed significant reduction in plasma ACE activity accompanied by a decrease in serum aldosterone levels. Moreover, significant changes in fetal development were observed, including growth retardation and renal damage after 20 days of gestation. Thus, data presented demonstrate the significant effects of the use of HETM on fetal development during pregnancy.

Offspring sex determines the impact of the maternal ACE I/D polymorphism on maternal glycaemic control during the last weeks of pregnancy

HYPOTHESIS/ INTRODUCTION: : We recently demonstrated that fetal sex may affect maternal glycaemic control in genetically prone mothers. We tested the hypothesis that fetal sex/fetal Y/X chromosomes might affect maternal glycaemic control during pregnancy depending on the maternal angiotensin converting enzyme (ACE) I/D polymorphism. : One thousand, three hundred and thirty-two Caucasian women without pre-existing diabetes and pre-existing hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycaemic control was analysed by measuring total glycated haemoglobin at birth. Correction for confounding factors and multiple testing was done. : Maternal ACE I/D polymorphism showed significant interaction with fetal sex concerning maternal total glycated haemoglobin. Total glycated haemoglobin in DD mothers delivering boys was 6.42 ± 0.70% vs. 6.21 ± 0.66% in DD mother delivering girls (p < 0.005), whereas the II carrying mothers showed the opposite effect. II mothers delivering a girl had a higher (p = 0.044) total glycated haemoglobin at birth (6.40 ± 0.80%) compared to II mothers delivering boys (6.21 ± 0.81%). There was no interaction of the ACE I/D polymorphism and fetal sex with respect to new onset proteinuria, new onset edema and pregnancy-induced hypertension. : Maternal glycaemic control during the last weeks of pregnancy seems to be influenced by an interaction of the ACE I/D genotyp and fetal sex.

Maternal and fetal angiotensin-converting enzyme gene insertion/deletion polymorphism not associated with pregnancy-induced hypertension in Chinese women

Objective. The study aimed to investigate whether maternal and fetal angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and the incompatibility of maternal and fetal ACE genotype are associated with the risk of pregnancy-induced hypertension (PIH) in Chinese Han women.Methods. Using a case-control mother-baby dyads study, a total of 226 maternal/offspring pairs were selected at Anyang Maternal and Child Health Hospital from January 2008 to December 2009. Maternal venous and cord bloods were obtained for DNA extraction. A polymerase chain reaction was performed on the genomic DNA samples to obtain the ACE gene I/D polymorphism.Results. In the present sample, there is no difference in maternal and fetal ACE genotype or allele frequency between PIH patients and control group (p > 0.05). Furthermore, no significant association was found between the genotype incompatibility of fetal and maternal ACE gene and the risk of PIH (p > 0.05).Conclusion. We did not find fetus ACE gene I/D polymorphism to be associated with the risk of PIH. Nor is there any evidence that the incompatibility of fetal and maternal ACE genotype is associated with PIH in the studied population.

Polymorphisms of the angiotensin converting enzyme gene in relation to intrauterine growth restriction

The aim of this case-control study was to explore the relation between maternal and infant angiotensin converting enzyme (ACE) activity and its genotypes in uncomplicated term pregnancies (> or =37 weeks) and pregnancies with growth-restricted infants (birthweight at or below the 5th centile). Venous cord bloods and maternal venous samples were obtained for serum ACE activity and ACE genotype. Growth-restricted infants (< or =5th centile) were more likely to be of the DD genotype compared to appropriately grown infants (42 vs. 13%, p = 0.003). There was no significant difference in the frequency of the maternal DD genotype between the two groups (33 vs. 22%, p = 0.43) and similarly no significant differences in the maternal or fetal ACE activities. Within the intrauterine growth restriction (IUGR) group, infants of the DD genotype had higher ACE activity compared to appropriately grown infants (p = 0.03). In conclusion, the DD genotype of the ACE gene appears to be associated with fetal growth and may be a factor in the increased risk of adult onset chronic diseases among growth-restricted infants.

Polymorphisms of the angiotensin converting enzyme gene in early-onset and late-onset pre-eclampsia

Objective. The aim of this study was to investigate differences in maternal and infant ACE genotypes in early-onset and later-onset pre-eclampsia/toxemia (PET).Methods. We conducted a case–control study of 22 cases of early-onset pre-eclampsia (before 34 weeks gestation), 38 cases of later-onset pre-eclampsia (after 34 weeks gestation), and 108 healthy controls delivered at term (38–40 weeks gestation) within a stable Caucasian population. Maternal venous blood and cord bloods were obtained for serum angiotensin converting enzyme (ACE) activity, ACE genotype, and acid–base status.Results. Mothers who developed early-onset PET were more likely to be homozygous for the deletion allele of the ACE genotype (DD) than mothers with late-onset PET or uncomplicated pregnancies (12/22 (55%) vs. 7/38 (18%) vs. 22/105 (21%), respectively; OR 2.96 [95% confidence intervals (CI) 1.37–6.31]. Infants of mothers with early-onset PET were more likely to be homozygous for the DD genotype than infants of mothers with late-onset PET or controls (7/19 (37%) vs. 9/36 (25%) vs. 11/78 (14%); OR 2.51 (95% CI 1.12–5.61). There were no differences in maternal or infant ACE activities in relation to onset of pre-eclampsia.Conclusions. Our findings suggest an association between the DD genotype of the ACE gene and early-onset but not later-onset pre-eclampsia which may give a partial explanation for the higher recurrence risk with early-onset pre-eclampsia.

Correlation of angiotensin converting enzyme activity and the genotypes of the I/D polymorphism in the ACE gene with preterm birth and birth weight

Objective Preterm birth remains one of the most challenging areas in obstetrics. The pathogenesis of preterm labor is multifactorial and research on preterm birth has focused principally on infection and inflammatory markers. Recently the focus has turned to potential genetic factors influencing preterm birth. Uteroplacental insufficiency and thrombotic vasculopathy are considered part of the pathogenesis of preterm labor. Investigating the gene expression in the maternal/fetal interface seems of importance to expand our knowledge of the pathophysiology of preterm birth. The renin–angiotensin system (RAS) appears to play an important role in fetal/placental development and uteroplacental circulation. Hence, the aim of this study was to investigate angiotensin converting enzyme (ACE) activity and I/D polymorphisms in the ACE gene in mothers and infants with appropriately grown infants in relation to preterm birth and infant birth weight. Study design We conducted a cross-sectional study of 113 term pregnancies (≥37 weeks) and 18 preterm pregnancies (<37 weeks). Umbilical cord bloods (venous and arterial) were obtained from the placenta immediately after delivery for serum ACE activity, ACE genotype analysis of the I/D polymorphism and the acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. Results The distribution of the maternal ACE genotypes was similar for preterm and term births as was maternal ACE activity. Preterm infants were more likely to be of the DD genotype than term infants (7/18 (39%) vs. 11/83 (13%), p = 0.02) (adjusted p = 0.04). There was no correlation between ACE activity and birth weight ( r 2 0.00, p = 0.82). Conclusions These findings suggest that the ACE genotype of the infant may influence the risk of preterm birth among appropriately grown fetuses.

The influence of mode of delivery and ACE genotype on serum angiotensin converting enzyme (ACE) activity in the mother and infant at term

Objective Angiotensin converting enzyme (ACE) and its genotype have been shown to play a role in the pathophysiology of pregnancy complications such as pre-eclampsia and intrauterine growth restriction and possibly in adult onset chronic diseases. The physiological changes of ACE and the influence of its genotype during the intrapartum period are not well known. Hence the aim of this study was to assess serum ACE activity and its genotype in mothers and infants at term in relation to labour and mode of delivery. Study design A cross sectional study of 99 women who laboured and 27 women who delivered by elective caesarean section after 36 completed weeks gestation with uncomplicated pregnancies. Venous cord bloods were obtained immediately after delivery of the placenta for serum ACE activity, ACE genotype and acid–base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. Univariate analyses were performed using parametric tests for normally distributed data and nonparametric tests for the data that were not normally distributed. A multiple regression model was developed to adjust for potential confounding factors. Results The umbilical venous ACE activity was similar for infants delivered following labour compared to those delivered by elective caesarean section, 47.2 U/L (35–64) versus 40.1 U/L (31–60) (adjusted p = 0.21). Maternal ACE activities were 28.9 U/L (22–35) and 32.1 U/L (22–40) respectively (adjusted p = 0.17). The ACE activity in infants was higher than that of mothers 46 U/L versus 22 U/L, respectively ( p = <0.001). Neither the mode of delivery nor the presence of suspected fetal compromise influenced maternal or infant ACE activity. There was no influence of the infants’ genotype on ACE activity in relation to mode of delivery. The DD genotype was associated with higher ACE activity in mothers ( p = 0.001) but not in infants ( p = 0.56). Conclusions This study shows that intrapartum events do not affect ACE activity. These results will enhance our ability to investigate the role of ACE and its genotype in abnormal fetal growth and in subsequent adult onset chronic disease.

Polymorphisms in the Angiotensin Converting Enzyme Gene and Growth in the First Year of Life

Abnormal patterns of fetal and infant growth have been associated with an increased risk of cardiovascular disease in adulthood. Catch-up growth during the first year of life has been associated with a higher prevalence of type 2 diabetes mellitus, whereas a lack of catch-up growth tracks with a risk of hypertension. The role of genetic factors influencing both growth and blood pressure have not been explored. We genotyped cord blood samples from 530 singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of 1650 pregnancies, and related polymorphism in the angiotensin converting enzyme (ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth and at age of 1 year. ACE genotype did not significantly influence size at birth, although there was a greater proportion of individuals with the D/D genotype born with a birth weight less than the 10th centile (P=0.004). The ACE I/I genotype was significantly associated with higher weight (p=0.001), body mass index (p=0.001) and mid arm circumference (p=0.001) at 1 year of age compared to the ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch-up (gain from birth size of >or=0.6 Standard Deviation Score) in weight (p=0.04), body mass index (p=0.03) and mid arm circumference (p=0.03) compared to the D/D group, the majority of which showed no change or catch-down. The I/D genotype was distributed equally across the catch up/catch down/no change categories. The effect was more marked in males, but ACE genotype and sex of the infant contributed independently to mid arm circumference measurements and there was no interaction between the two. There was no effect of maternal or paternal ACE genotype on birth size. In a multiple linear regression model ACE genotype, socioeconomic status and sex of the infant explained 10.9% of the variance in body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is associated with a higher weight and body mass index SDS at 1 year of age, along with catch-up in terms of these measures from birth to 1 year. The D/D genotype is associated with a greater proportion of babies, born at term, that at small for gestational age. These results suggest that due consideration should be given to the underlying genotype of an individual when evaluating the association of early human growth with the development of risk factors for cardiovascular disease. The observation of independent effects of genotype, sex of the individual and socioeconomic status on postnatal growth suggests the need to develop methodologies for the integration of genetic and environmental factors in causality modelling.

Angiotensin converting enzyme activity in infancy is related to birth weight

Aims: (a) To measure infant angiotensin converting enzyme (ACE) activity in healthy term infants at birth and during the first three months of life. (b) To determine the relation between...

Angiotensin-converting enzyme activity in pre-eclampsia

This paper summarizes a study that aimed to estimate maternal and umbilical serum angiotensin-converting enzyme (ACE) activity in singleton pregnancies complicated by preeclampsia. This study was carried out at the University Medical School of Lublin in Poland on 17 patients with singleton pregnancy complicated by preeclampsia between 33 and 40 weeks of gestation. Meanwhile the control group consisted of 14 healthy normotensive patients with singleton uncomplicated pregnancy and normal laboratory tests. The serum ACE activity was estimated using spectrophotometry. It was noted that there were no statistically significant differences in patients profiles between groups in gravidity parity maternal age gestational age and the mode of delivery. Overall the study revealed elevated maternal and umbilical serum ACE activity in pregnancies complicated by preeclampsia. Hence it indicates a significant role of ACE in pregnancy complicated by preeclampsia.

Fetal, neonatal cord, and maternal plasma concentrations of angiotensin-converting enzyme (ACE).

Angiotensin converting enzyme (ACE), a component of the renin-angiotensin system (RAS), catalyses the degradation of angiotensin I to angiotensin II. It was the aim of the present study to measure ACE activity in human fetal blood and to determine its changes with advancing gestational age. Fetal blood was sampled by cordocentesis from six control fetuses and six fetuses with Rh isoimmunisation. Cord blood was sampled from six preterm neonates, 15 neonates after spontaneous delivery at term and six neonates at term after caesarean section. In addition, maternal ACE values were determined. ACE activity was measured using the miniaturised fluorimetric method. In normal fetuses (13.31+/-1.41 nmol HL/min/ml) and fetuses with Rh isoimmunisation (13.08+/-2.00 nmol HL/min/ml, p<0.05). Neonatal cord blood of preterm newborns (10.43+/-0.69 nmol HL/min/ml) and term newborns (8.99+/-0.49 nmol HL/min/ml) showed a significantly decreased ACE activity compared to the fetal controls. We conclude that the high fetal ACE activity and the stringent regulation with advancing gestational age indicate the physiological importance of the enzyme during prenatal development.

Developmental changes in plasma angiotensin-converting enzyme concentration in fetal and neonatal lambs.

Relationships between plasma angiotensin-converting enzyme (ACE) and cortisol, and blood pressure were examined in chronically catheterized ewes and their fetuses during late gestation (111-141 days, term 145 +/- 2 days). Plasma ACE was also measured in non-pregnant adult ewes and in lambs over the first 5 weeks of life. In fetuses near term (136-141 days), plasma ACE was greater than in those studied earlier in gestation; overall, plasma ACE correlated with gestational age (r = 0.72). The ontogenic rise in plasma ACE was associated with prepartum increases in plasma cortisol (r = 0.67) and blood pressure (r = 0.66). No relationship was observed between plasma ACE and partial pressure of oxygen in utero. Peak plasma ACE concentration observed in fetuses near term was maintained in newborn lambs for 3 days after birth. By 2 weeks of postnatal age, plasma ACE had decreased to the value seen in non-pregnant adult ewes. Maternal plasma ACE was similar at all gestational ages studied, and was lower than that observed in non-pregnant ewes. Therefore, in the sheep fetus, plasma ACE increased towards term in association with the prepartum cortisol surge. Developmental changes in ACE activity may be partly responsible for the ontogenic rise in fetal blood pressure.

The effect of enalapril (MK421), an angiotensin converting enzyme inhibitor, on the conscious pregnant ewe and her foetus.

The effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, on maternal and foetal blood pressure, heart rate and components of the renin-angiotensin-aldosterone system were studied in 9 chronically-cannulated pregnant ewes and their foetuses. Six ewes received 1 mg kg-1 enalapril i.v. while 3 were given 2 mg kg-1. Although the initial fall in blood pressure was slightly greater in the higher dose group, there was substantial overlap of data. The pressor response to angiotensin I, assessing ACE activity, was abolished within 10 min of administration, and did not recover during 3 h of observation. Maternal systolic and diastolic pressures reached a nadir 90 min after administration (P less than 0.001, P less than 0.002 respectively). The maximum tachycardia was seen at 60 min (P less than 0.05). The foetuses of the ewes given 1 mg kg-1 enalapril showed no change in systolic or diastolic blood pressure or heart rate. Those of the ewes given the higher dose showed late-onset hypotension, coincident with the lowest maternal blood pressures. Maternal plasma renin concentration (PRC) had risen significantly by 30 min (P less than 0.02), reaching a maximum at approximately 90 min. Maternal plasma angiotensin II and aldosterone concentrations both fell initially (P less than 0.05) but were almost at basal levels by the end of the experiment. Foetal plasma renin, angiotensin II and aldosterone concentrations were unchanged throughout the experiment. Peak values of enaprilic acid, the active principle, were recorded in maternal plasma 65-90 min after administration of 1 mg kg-1, and 25-30 min after the administration of 2 mg kg-1. A trace amount of the active principle was recorded in the foetal plasma of one lamb, whose mother had been given the higher dose. None was recorded in the plasma from three other lambs. Maternal plasma ACE concentrations fell by an average of 84%; in 4 of the 6 ewes in which concentrations were measured they were undetectable after treatment. Foetal plasma ACE concentrations were unchanged throughout. Enalapril at 1 mg kg-1 thus exerts a depressor effect on the pregnant ewe which is probably related to its blockade of the renin-angiotensin system. Both direct measurement of the drug and foetal observation suggest that it does not cross the sheep placenta at this dose. This is consistent with its failure to cross the blood-brain barrier. Foetal effects were noted at 2 mg kg-1, and there was an unexpected foetal death in this group.

A prospective study of plasma angiotensin-converting enzyme in normotensive primigravidae and their infants.

Plasma angiotensin-converting enzyme (ACE) has been measured prospectively throughout pregnancy, at delivery and in the puerperium in 18 normotensive primigravidae and their infants. Plasma ACE was consistently lower during pregnancy than in comparable, non-pregnant controls, but rose progressively from about 30 weeks to term. At vaginal delivery maternal and fetal ACE levels did not differ significantly. There was a steady increase in maternal ACE activity up to 6 weeks post partum, when the levels were not significantly different from non-pregnant controls. No correlation could be found between plasma ACE and plasma renin activity or concentration, or plasma AII. Plasma aldosterone increased in parallel with ACE during the last ten weeks of pregnancy.