المؤلفون: Irene Mackraj, Jagidesa Moodley, Saravanakumar Murugesan, Olive P. Khaliq

المصدر: Clinical and Experimental Hypertension. 40:744-751

مصطلحات موضوعية: Adult, 0301 basic medicine, Gestational hypertension, medicine.medical_specialty, Physiology, Placenta, Blood Pressure, 030204 cardiovascular system & hematology, Real-Time Polymerase Chain Reaction, Preeclampsia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pre-Eclampsia, Western blot, Pregnancy, Internal medicine, microRNA, Internal Medicine, medicine, Humans, Insulin, Differential expression, Protein kinase B, PI3K/AKT/mTOR pathway, medicine.diagnostic_test, business.industry, Hypertension, Pregnancy-Induced, General Medicine, medicine.disease, MicroRNAs, 030104 developmental biology, Endocrinology, Gestation, Female, Phosphatidylinositol 3-Kinase, business, Proto-Oncogene Proteins c-akt, Signal Transduction

الوصف: The objective of this study was to determine microRNAs (miRNAs) expression levels in placental tissue and serum samples from preeclampsia (PE) and gestational hypertensive (GH) patients.Using a targeted qPCR method, the selected miRNAs putatively involved in the PE and GH were examined from normotensive (n = 32), PE (n = 32) and GH (n = 28) in South African women. Western blot analysis of protein expressions of AKT and PI3K was performed in the placental tissue of all three groups.qPCR results of serum miR-222 expression levels showed a significant decrease in PE compared to GH and normotensive groups. miR-29a expression levels were significantly increased in PE and GH groups compared to normotensives. Serum expression levels of miR-181a in GH showed a significant increase compared to the PE and normotensive groups. Placental tissue expression levels of miR-181a were significantly increased in PE and GH groups compared to normotensives. Western blot results of placental tissue showed a decrease in the expression levels of AKT-serine and threonine in the PE groups compared to the normotensives and a significantly higher expression in the GH groups compared to normotensives. Phosphatidyl-inositol-3 kinase (PI3K) expression levels were significantly decreased in PE and GH groups compared to normotensives.The present study, interestingly, demonstrates the differential expression of circulating miRNA in GH and a correlation between the expression levels of miRNAs with AKT/PI3K in the insulin signaling pathway, reinforcing the presence of metabolic dysregulation in PE and GH.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46405b5d53b00e9c1ae4854752819262Test
https://doi.org/10.1080/10641963.2018.1431257Test

المؤلفون: Wendy N. Phoswa, Prem Gathiram, Jagidesa Moodley, Saravanakumar Murugesan, Irene Mackraj, Nerolen Soobryan

المصدر: European Journal of Pharmacology. 795:101-107

مصطلحات موضوعية: Vascular Endothelial Growth Factor A, medicine.medical_specialty, Time Factors, Sildenafil, Neovascularization, Physiologic, Blood Pressure, 030204 cardiovascular system & hematology, Nitric Oxide, Sildenafil Citrate, Nitric oxide, Rats, Sprague-Dawley, Lipid peroxidation, Interferon-gamma, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pre-Eclampsia, Pregnancy, Transforming Growth Factor beta, Internal medicine, Placenta, medicine, Animals, RNA, Messenger, Inflammation, Pharmacology, Fetus, Vascular Endothelial Growth Factor Receptor-1, 030219 obstetrics & reproductive medicine, Eclampsia, business.industry, Uterus, medicine.disease, Rats, Disease Models, Animal, NG-Nitroarginine Methyl Ester, Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, chemistry, Gestation, Female, business, Biomarkers, Soluble fms-like tyrosine kinase-1

الوصف: Pre-eclampsia (PE), a hypertensive disorder of pregnancy, is detrimental to both mother and foetus. There is currently no effective treatment, but we have shown that Sildenafil Citrate (SC) improve various foetal outcomes in Nω-nitro-L arginine methyl ester (L-NAME) rat model of PE. Therefore, we aimed to investigate the effects of SC on a uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of PE. One hundred and twenty adult nulliparous pregnant female Sprague-Dawley rats were used for the study. These were divided into five equal groups; the pregnant control, early and late onset PE and respective SC treated animals. Hypertension was manifested by considerably increased systolic blood pressure and placental lipid peroxidative marker (thiobarbituric acid reactive substances) and also we assessed the activities of plasma nitric oxide level, serum inflammatory marker (TGF-β and IFN-γ) and uterine angiogenic status (VEGF and sFlt-1) at two stages of PE. The administration of SC decreased systolic blood pressure, placental lipid peroxidation product and altered uterine angiogenic status; increased plasma nitric oxide levels in an early and late onset L-NAME model of PE. In addition, histological findings of SC treated preeclamptic rat placenta support the biochemical findings of this study. Our findings revealed that SC enhanced plasma NO levels and uterine angiogenic status in an L-NAME model of PE at two gestational stages.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::153cf46b1d2ed255ca6ae82e3a4f29aeTest
https://doi.org/10.1016/j.ejphar.2016.12.010Test

المؤلفون: Nerolen Soobryan, Arunagiri Pandiyan, Saravanakumar Murugesan, Jagidesa Moodley, Irene Mackraj

المصدر: Reproductive sciences (Thousand Oaks, Calif.). 25(11)

مصطلحات موضوعية: Gestational hypertension, Placenta, 030204 cardiovascular system & hematology, Bioinformatics, Preeclampsia, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Diabetes mellitus, medicine, Animals, Humans, Hypoglycemic Agents, Endothelial dysfunction, 030219 obstetrics & reproductive medicine, Eclampsia, Neovascularization, Pathologic, business.industry, Obstetrics and Gynecology, Endothelial Cells, Hypertension, Pregnancy-Induced, medicine.disease, Metformin, Polycystic ovarian disease, Angiogenesis Inducing Agents, Female, Insulin Resistance, business, medicine.drug

الوصف: In the face of escalating maternal and fetal health threats, hypertensive pregnancy disorders (HPDs) is one of the leading cause of maternal and fetal morbidity and mortality. The range of HPDs include white-coat hypertension, chronic hypertension, gestational hypertension, mild-to-moderate and severe preeclampsia and eclampsia. Current evidence implicates an imbalance of circulating anti- and angiogenic factors in HPDs emanating from the placental vasculature, impacting on angiogenesis. Delivery of the fetus is thus far the only curative measure, albeit with increased risk. Resultant endothelial dysfunction caused by the excessive production of placental soluble fms-like tyrosine kinase-1 has been the basis of many studies to find a safer treatment strategy. Metformin, used historically in the treatment of diabetes mellitus has also found its therapeutic reach in many other disease states. These include, but are not limited to, improving blood flow in certain cancer types, treatment of polycystic ovarian disease, improving vasodilation, and reducing inflammation. Metformin is used to treat hyperglycemic endothelial dysfunction through the enhancement of the nitric oxide system, endothelin-derived hyperpolarizing factor and sirtuin 1. Similarly, endothelial dysfunction in preeclampsia and other HPDs leads to a hypoxic state and elevated blood pressures. Dubbed as the new "aspirin" of current times, the retardation of the antiangiogenic status by metformin provides an exciting and promising alternate strategy in treating these pregnancy disorders.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5259106dbb5fd7bf4429a28ae19caba1Test
https://pubmed.ncbi.nlm.nih.gov/29739273Test