The goal was to assess how a history of any kind of pregnancy-related complication altered expression profile of microRNAs played a role in the pathogenesis of diabetes, cardiovascular and cerebrovascular diseases in the peripheral blood leukocytes of children at the age of 3-11 years. The prior exposure to gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes or spontaneous preterm birth causes that a significant proportion of children (57.42% to 90.0% specifically) had a substantially altered microRNA expression profile, which might be the origin of a lifelong cardiovascular risk. A total of 23 out of 29 tested microRNAs were upregulated in children born from such complicated gestation. The occurrence of overweight, obesity, valve problems and heart defects even intensified upregulation of microRNAs already present in children exposed to such pregnancy complications. The occurrence of overweight/obesity (miR-92a-3p, and miR-210-3p) and valve problems or heart defects (miR-342-3p) induced microRNA upregulation in children affected with pregnancy complications. Overall, 42.86% overweight/obese children and 27.36% children with valve problems or heart defects had even higher microRNA levels than children with normal clinical findings after complicated pregnancies. In addition, the microRNA expression profile was also able to differentiate between children descending from normal gestation in relation to the occurrence of overweight and obesity. Screening on the base of the combination of 19 microRNAs identified 70.0% overweight/obese children at 90.0% specificity. In general, children after complicated pregnancies, just as children after normal pregnancies, with abnormal findings are at a higher risk of the onset of cardiovascular complications, and their dispensarization, with the aim to implement primary prevention strategies, would be beneficial.

• MeSH
• cerebrovaskulární poruchy genetika   MeSH
• dítě MeSH
• dospělí MeSH
• gestační diabetes genetika   MeSH
• hypertenze indukovaná těhotenstvím genetika   MeSH
• hypertenze genetika   MeSH
• incidence MeSH
• kardiovaskulární nemoci genetika   MeSH
• komplikace těhotenství genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• mladý dospělý MeSH
• nadváha genetika   MeSH
• obezita genetika   MeSH
• předškolní dítě MeSH
• preeklampsie genetika   MeSH
• prehypertenze genetika   MeSH
• prospektivní studie MeSH
• růstová retardace plodu genetika   MeSH
• těhotenství MeSH
• upregulace genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND METHODS: Gestational hypertension (GH), preeclampsia (PE) and fetal growth restriction (FGR) may predispose to later onset of cardiovascular/cerebrovascular diseases. We examined if pregnancy complications induce postpartum alterations in gene expression of cardiovascular/cerebrovascular disease associated microRNAs. 29 microRNAs were tested in peripheral blood of women, compared between groups with a history of GH, PE, FGR and controls, and correlated with the severity of the disease regarding clinical signs, delivery date, and Doppler parameters. RESULTS: GH was associated with the up-regulation of miR-20a-5p, miR-143-3p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. The up-regulation of miR-17-5p, miR-20b-5p, miR-29a-3p, and miR-126-3p was a mutual phenomenon of GH and severe PE. GH and early PE were associated with up-regulation of miR-1-3p and miR-17-5p. GH and late PE showed up-regulation of miR-17-5p, miR-20b-5p, and miR-29a-3p. Severe PE induced up-regulation of miR-133a-3p and down-regulation of miR-130b-3p. MiR-133a-3p up-regulation was also observed in early PE. PE and/or FGR with abnormal Doppler parameters demonstrated up-regulation of miR-100-5p, miR-125b-5p, miR-133a-3p, and miR-145-5p. The combination screening was superior over using individual microRNAs for patients with GH, PE regardless of the severity of the disease, severe PE and early PE. A cardiovascular risk at patients with late PE, PE and/or FGR with abnormal Doppler parameters was identified more accurately using the single microRNA only. CONCLUSION: Epigenetic changes characteristic for cardiovascular/cerebrovascular diseases are present in women with a prior exposure to pregnancy complications. Screening of microRNAs may be used to identify patients at a higher risk of later development of cardiovascular/cerebrovascular diseases.

• MeSH
• cerebrovaskulární poruchy diagnóza   genetika   MeSH
• dospělí MeSH
• genetický profil MeSH
• hypertenze indukovaná těhotenstvím diagnóza   genetika   MeSH
• kardiovaskulární nemoci diagnóza   genetika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• následné studie MeSH
• pilotní projekty MeSH
• poporodní období genetika   MeSH
• preeklampsie diagnóza   genetika   MeSH
• prospektivní studie MeSH
• růstová retardace plodu diagnóza   genetika   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 29 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in maternal whole peripheral blood, compared between groups (39 gestational hypertension, 68 preeclampsia, 33 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in patients affected by pregnancy-related complications have been carried out. RESULTS: The expression profile of microRNAs was different between pregnancy-related complications and controls. The down-regulation of miR-100-5p, miR-125b-5p and miR-199a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Moreover, IUGR pregnancies induced down-regulation of miR-17-5p, miR-146a-5p, miR-221-3p and miR-574-3p in maternal circulation. Irrespective of the severity of the disease, preeclampsia was associated with the dysregulation of miR-100-5p and miR-125b-5p and IUGR with dysregulation of miR-199a-5p. Preeclampsia requiring termination of gestation before 34 weeks was associated with down-regulation of miR-146a-5p, miR-199a-5p and miR-221-3p. Weak negative correlation between miR-146a-5p and miR-221-3p expression and the pulsatility index in the umbilical artery was found. Additional microRNAs (miR-103a-3p, miR-126-3p, miR-195-5p and miR-499a-5p) showed a trend to down-regulation in appropriate pregnancy-related complications. CONCLUSION: Epigenetic changes are induced by pregnancy-related complications in maternal whole peripheral blood.

• MeSH
• cerebrovaskulární poruchy krev   genetika   MeSH
• dospělí MeSH
• epigeneze genetická genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• hypertenze indukovaná těhotenstvím krev   genetika   MeSH
• kardiovaskulární nemoci krev   genetika   MeSH
• lidé MeSH
• mikro RNA krev   genetika   MeSH
• preeklampsie krev   genetika   MeSH
• růstová retardace plodu krev   genetika   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 32 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-33a-5p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-208a-3p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in placental tissues, compared between groups (35 gestational hypertension, 80 preeclampsia, 35 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in placental tissues affected by pregnancy-related complications have been carried out. RESULTS: The expression profile of microRNAs was different between pregnancy-related complications and controls. The up-regulation of miR-499a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Preeclamptic pregnancies delivering after 34 weeks of gestation and IUGR with abnormal values of flow rate in the umbilical artery demonstrated up-regulation of miR-1-3b. Preeclampsia and IUGR requiring termination of gestation before 34 weeks of gestation were associated with down-regulation of miR-26a-5p, miR-103a-3p and miR-145-5p. On the other hand, some of microRNAs (miR-16-5p, miR-100-5p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-143-3p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, and miR-574-3p) were only down-regulated or showed a trend to down-regulation just in intrauterine growth restriction pregnancies requiring the delivery before 34 weeks of gestation. CONCLUSION: Epigenetic changes induced by pregnancy-related complications in placental tissue may cause later onset of cardiovascular and cerebrovascular diseases in offspring.

• MeSH
• cerebrovaskulární poruchy diagnóza   genetika   MeSH
• dospělí MeSH
• down regulace MeSH
• gestační stáří MeSH
• hypertenze indukovaná těhotenstvím diagnóza   genetika   MeSH
• komplikace těhotenství MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• mikro RNA analýza   metabolismus   MeSH
• nemoci cév diagnóza   genetika   MeSH
• placenta metabolismus   MeSH
• preeklampsie diagnóza   genetika   MeSH
• růstová retardace plodu diagnóza   genetika   MeSH
• těhotenství MeSH
• transkriptom MeSH
• ultrasonografie dopplerovská MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: The objective of the study was to evaluate risk assessment for gestational hypertension based on the profile of circulating placental specific C19MC microRNAs in early pregnancy. STUDY DESIGN: The prospective longitudinal cohort study of women enrolled at first trimester screening at 10 to 13 weeks was carried out (n = 267). Relative quantification of placental specific C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) was determined in 28 normal pregnancies and 18 pregnancies which developed gestational hypertension using real-time PCR and a comparative Ct method relative to synthetic C. elegans microRNA (cel-miR-39). RESULTS: Increased extracellular C19MC microRNA plasmatic levels (miR-516-5p, p<0.001; miR-517*, p = 0.007; miR-520h, p<0.001; miR-518b, p = 0.002) were detected in patients destined to develop gestational hypertension. MiR-520h had the best predictive performance with a PPV of 84.6% at a 7.1% false positive rate. The combination of miR-520h and miR-518b was able to predict 82.6% of women at the same false positive rate. The overall predictive capacity of single miR-518b (73.3% at 14.3% FPR), miR-516-5p (70.6% at 17.9% FPR) and miR-517* (57.9% at 28.6% FPR) biomarkers was lower. CONCLUSION: The study brought interesting finding that the up-regulation of miR-516-5p, miR-517*, miR-520h and miR-518b is associated with a risk of later development of gestational hypertension. First trimester screening of extracellular miR-520h alone or in combination with miR-518b identified a significant proportion of women with subsequent gestational hypertension.

• MeSH
• Caenorhabditis elegans MeSH
• hypertenze indukovaná těhotenstvím krev   genetika   patologie   MeSH
• lidé MeSH
• lidské chromozomy, pár 19 MeSH
• mikro RNA krev   genetika   MeSH
• placenta patologie   MeSH
• prospektivní studie MeSH
• první trimestr těhotenství MeSH
• sekvence nukleotidů MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The objective of the study was to identify the profile of circulating C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a) in patients with established preeclampsia (n = 63), fetal growth restriction (n = 27), and gestational hypertension (n = 23). We examined the correlation between plasmatic concentrations and expression levels of microRNAs and the severity of the disease with respect to clinical signs, requirements for the delivery, and Doppler ultrasound parameters. Using absolute and relative quantification approaches, increased extracellular C19MC microRNA levels (miR-516-5p, P = 0.037, P = 0.009; miR-517*, P = 0.033, P = 0.043; miR-520a*, P = 0.001, P = 0.009; miR-525, P = 0.026, P = 0.01; miR-526a, P = 0.03, P = 0.035) were detected in patients with preeclampsia. The association analysis pointed to no relationship between C19MC microRNA plasmatic concentrations and expression profile and identified risk factors for a poorer perinatal outcome. However, the dependence between the levels of plasmatic C19MC microRNAs and the pulsatility index in the middle cerebral artery and the values of cerebroplacental ratio was demonstrated. The study brought the interesting finding that the upregulation of miR-516-5p, miR-517*, miR-520a*, miR-525, and miR-526a is a characteristic phenomenon of established preeclampsia.

• MeSH
• hypertenze indukovaná těhotenstvím genetika   MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• preeklampsie genetika   MeSH
• regulace genové exprese MeSH
• růstová retardace plodu genetika   MeSH
• stupeň závažnosti nemoci MeSH
• těhotenství krev   MeSH
• ultrasonografie dopplerovská MeSH
• Check Tag
• lidé MeSH
• těhotenství krev   MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH