- Email: [email protected]
[269-POS]
134
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 53–156
Objectives: Therapy with nitric oxide (NO) donors in addition with plasma volume expansion in pregnancy complicated by fetal growth restriction (FGR) could improve pregnancy outcome. Aim of our study was to identify a good marker showing the improvement in fetal growth and maternal hemodynamics. Methods: A prospective case-control study was conducted. We followed 40 women with singleton pregnancy between 28 and 30 weeks of gestation with diagnosis of FGR (abdominal circumference CA < 5°pc) and Systemic Vascular Resistance (SVR) > 1200 dynes.sec.cm-5, divided in two groups: Group A, treated with transdermal patches of NO donors (5 mg/24 h) and oral fluids (2–3 lt) and Group B treated with oral fluids only. We evaluated SVR, cardiac output (CO), inotropy index (INO) and the trend of abdominal circumference percentile at the diagnosis, after 2 and 4 weeks of treatment. We obtained the hemodynamic measurements with the USCOM system. Results: Group A showed an increase in CO (+14% after 2 weeks and +8% after 4 weeks), an increase in INO (+29% and +2%) and a decrease in SVR ( 12% and 9%). A significant improvement in abdominal circumference percentile was shown (increase of 44% after 2 weeks and 33% after 4 weeks). Group B showed a small increase in SVR (+1% after 2 weeks and +2% after 4 weeks), stable values of INO and CO ( 4% and +5% for INO and 1% and +1% for CO), and a reduction in CA percentile ( 16% and 18%). Conclusions: CO, SVR and INO showed an improvement consonant with the trend of abdominal circumference percentile; they could be a good method to evaluate the prolongation of gestation and the increase in fetal growth.
Department of Obstetrics and Gynecology, Semmelweis b University, Budapest, Hungary, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, c First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary) Objectives: The endocannabinoid system plays a key role in female reproduction, including implantation, decidualization and placentation. In the present study, we aimed to analyze cannabinoid receptor 1 (CB1), CB2 and fatty acid amid hydrolase (FAAH) expressions and localization in normal and preeclamptic placenta, in order to determine whether aberrant endocannabinoid activity is related to preeclampsia. Methods: Eighteen preeclamptic patients and 18 normotensive, healthy pregnant women with uncomplicated pregnancies were involved in our case-control study. We determined CB1, CB2 and FAAH expressions by Western immunoblotting and immunohistochemistry in placental samples collected directly after Cesarean section. Results: CB1 expression measured by Western immunoblotting was significantly higher in preeclamptic placenta, and these findings were confirmed by immunohistochemistry. CB1 immunoreactivity was markedly stronger in syncytiotrophoblasts, the mesenchymal core, decidua, villous capillary endothelial and smooth muscle cells, as well as in the amnion in preeclamptic samples compared to normal pregnancies. However, we did not find significant differences between preeclamptic and normal placenta in terms of CB2 and FAAH expressions and immunoreactivity. Conclusions: We observed markedly higher expression of CB1 protein in preeclamptic placental tissue. Increased CB1 expression might cause abnormal decidualization and impair trophoblast invasion, thus being involved in the pathogenesis of preeclampsia. As CB1 activation can induce endothelial dysfunction and enhance vascular inflammation, the strong CB1 immunoreaction in vascular endothelial and smooth muscle cells suggests that CB1 may contribute to the development of atherosis in the placental villi shown earlier in preeclampsia. While the detailed pathogenesis of preeclampsia is still unclear, the endocannabinoid system could play a role in the development of the disease. Disclosures: A. Molvarec: None. G. Fügedi: None. M. Molnár: None. J. Schönléber: None. I. Kovalszky: None. J. Rigó: None.
Disclosures: G. Gagliardi: None. D. Lo Presti: None. G. Tiralongo: None. I. Pisani: None. R. Scala: None. G. Novelli: None. B. Vasapollo: None. H. Valensise: None.
doi:10.1016/j.preghy.2014.10.274
doi:10.1016/j.preghy.2014.10.273
[269-POS]
[268-POS] Placental expression of the endocannabinoid system in preeclampsia Attila Molvarec a, Gergely Fügedi a, Miklós Molnár b, Júlia Schönléber a, Ilona Kovalszky c, János Rigó Jr. a (a First
Utero-placental cellular and subcellular expression of opposing AT1R and B2R receptors in normal and preeclamptic pregnancies Gloria Valdes a, Stephanie Acuña a, Gloria X. Soto b (a Escuela Medicina Pontificia Universidad Catolica, Santiago, Chile, b Hospital San Borja Arriarán, Santiago, Chile)
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 53–156
Objectives: The main receptors of the antagonic reninangiotensin and kallikrein–kinin systems, AT1R and B2R, are expressed in villous and extravillous trophoblasts in normal and preeclamptic placentas, and have in vitro and in vivo effects related to placentation. Expecting a functional equilibrium in normal pregnancy and a disruption favouring vasoconstriction in preeclampsia, we studied the cellular/ subcellular localization and balance between AT1R and B2R in normal and preeclamptic pregnancies. Methods: Placentas, obtained from normotensive and preeclamptic pregnancies (n = 14 per group) at the San BorjaArriarán Hospital, were separated into villous zone and basal plate, and submitted to immunohistochemistry, WB and double-labeling immunoelectron microscopy using polyclonal and monoclonal anti-AT1R and B2R. Results: In the placenta of normal and preeclamptic pregnancies AT1R and B2R receptor immunoreactivity was expressed in syncytiotrophoblast and endothelium; the basal plate displayed reactivity for both receptors in extravillous trophoblasts and decidual cells. The protein content of AT1R and B2R (65 y 40 KDa respectively) was demonstrated in both placental zones. Neither the content of AT1R, B2R or the AT1R/B2R ratio differed between both groups. In immunoelectron microscopy AT1R and B2R were present in syncytiotrophoblast, extravillous cytotrophoblasts and decidual cells in the cell membrane, the rough endoplasmic reticulum and predominantly in the nucleus. Conclusions: This study demonstrates that the antagonic receptors AT1R and B2R colocalize in the syncytiotrophoblast, endotelium, extravillous trophoblast and decidual cells. Though a disrupted equilibrium between AT1R and B2R was not observed, the salient observation of their nuclear localization opens a new space of action for angiotensin II, bradykinin and especially for the AT1R agonistic autoantibody, posing the need to dissect their intranuclear functions.Grant Fondecyt 1121161.
135
(Osaka University Graduate School of Medicine, Suita, Japan) Objectives: In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin and that nicotine inhibits interleukin 6 (IL-6) productions which maternal serum stimulates. Methods: Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells (HUVECs) treated with nicotine, and with various combinations of soluble fms-like tyrosine kinase 1, soluble endoglin, and nicotine. Enzyme-linked immunosorbent assay (ELISA) was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor- 1 concentrations in the conditioned media treated with nicotine. HUVECs were incubated with or without 0.5% serum from healthy pregnant women at term and treated with or without nicotine in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. IL-6 concentration and nuclear transcription factor kappa B (NF-kB) activities were determined by ELISA-based method. Results: Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fmslike tyrosine kinase 1 and/or soluble endoglin reduced endothelial functions. Placental growth factor, but not transforming growth factor-1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable. IL-6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-kB activation in endothelial cells. Conclusions: Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia. Disclosures: K. Mimura: None. T. Tomimatsu: None. T. Kimura: None. doi:10.1016/j.preghy.2014.10.276
[271-POS] Disclosures: G. Valdes: None. S. Acuña: None. G.X. Soto: None. doi:10.1016/j.preghy.2014.10.275
[270-POS] A possible therapeutic role of nicotine for preeclampsia Kazuya Mimura, Takuji Tomimatsu, Tadashi Kimura
Glucocerebrosidase expression and activity in human placenta from normotensive and preeclamptic pregnancies Jiska M. Jebbink a, Rolf G. Boot b, Remco Keijser b, Perry D. Moerland b, Jan Aten b, Geertruda J. Veenboer b, Madelon van Wely b, Maarten Buimer b, Emiel Ver Loren van Themaat b, Johannes M. Aerts b, Joris A. van der Post b, Gijs B. Afink b, Carrie Ris-Stalpers b (a Onze Lieve Vrouwe Gasthuis & Academic Medical Center, Amsterdam, Netherlands, b Academic Medical Center, Amsterdam, Netherlands)
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 53–156
Objectives: Therapy with nitric oxide (NO) donors in addition with plasma volume expansion in pregnancy complicated by fetal growth restriction (FGR) could improve pregnancy outcome. Aim of our study was to identify a good marker showing the improvement in fetal growth and maternal hemodynamics. Methods: A prospective case-control study was conducted. We followed 40 women with singleton pregnancy between 28 and 30 weeks of gestation with diagnosis of FGR (abdominal circumference CA < 5°pc) and Systemic Vascular Resistance (SVR) > 1200 dynes.sec.cm-5, divided in two groups: Group A, treated with transdermal patches of NO donors (5 mg/24 h) and oral fluids (2–3 lt) and Group B treated with oral fluids only. We evaluated SVR, cardiac output (CO), inotropy index (INO) and the trend of abdominal circumference percentile at the diagnosis, after 2 and 4 weeks of treatment. We obtained the hemodynamic measurements with the USCOM system. Results: Group A showed an increase in CO (+14% after 2 weeks and +8% after 4 weeks), an increase in INO (+29% and +2%) and a decrease in SVR ( 12% and 9%). A significant improvement in abdominal circumference percentile was shown (increase of 44% after 2 weeks and 33% after 4 weeks). Group B showed a small increase in SVR (+1% after 2 weeks and +2% after 4 weeks), stable values of INO and CO ( 4% and +5% for INO and 1% and +1% for CO), and a reduction in CA percentile ( 16% and 18%). Conclusions: CO, SVR and INO showed an improvement consonant with the trend of abdominal circumference percentile; they could be a good method to evaluate the prolongation of gestation and the increase in fetal growth.
Department of Obstetrics and Gynecology, Semmelweis b University, Budapest, Hungary, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, c First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary) Objectives: The endocannabinoid system plays a key role in female reproduction, including implantation, decidualization and placentation. In the present study, we aimed to analyze cannabinoid receptor 1 (CB1), CB2 and fatty acid amid hydrolase (FAAH) expressions and localization in normal and preeclamptic placenta, in order to determine whether aberrant endocannabinoid activity is related to preeclampsia. Methods: Eighteen preeclamptic patients and 18 normotensive, healthy pregnant women with uncomplicated pregnancies were involved in our case-control study. We determined CB1, CB2 and FAAH expressions by Western immunoblotting and immunohistochemistry in placental samples collected directly after Cesarean section. Results: CB1 expression measured by Western immunoblotting was significantly higher in preeclamptic placenta, and these findings were confirmed by immunohistochemistry. CB1 immunoreactivity was markedly stronger in syncytiotrophoblasts, the mesenchymal core, decidua, villous capillary endothelial and smooth muscle cells, as well as in the amnion in preeclamptic samples compared to normal pregnancies. However, we did not find significant differences between preeclamptic and normal placenta in terms of CB2 and FAAH expressions and immunoreactivity. Conclusions: We observed markedly higher expression of CB1 protein in preeclamptic placental tissue. Increased CB1 expression might cause abnormal decidualization and impair trophoblast invasion, thus being involved in the pathogenesis of preeclampsia. As CB1 activation can induce endothelial dysfunction and enhance vascular inflammation, the strong CB1 immunoreaction in vascular endothelial and smooth muscle cells suggests that CB1 may contribute to the development of atherosis in the placental villi shown earlier in preeclampsia. While the detailed pathogenesis of preeclampsia is still unclear, the endocannabinoid system could play a role in the development of the disease. Disclosures: A. Molvarec: None. G. Fügedi: None. M. Molnár: None. J. Schönléber: None. I. Kovalszky: None. J. Rigó: None.
Disclosures: G. Gagliardi: None. D. Lo Presti: None. G. Tiralongo: None. I. Pisani: None. R. Scala: None. G. Novelli: None. B. Vasapollo: None. H. Valensise: None.
doi:10.1016/j.preghy.2014.10.274
doi:10.1016/j.preghy.2014.10.273
[269-POS]
[268-POS] Placental expression of the endocannabinoid system in preeclampsia Attila Molvarec a, Gergely Fügedi a, Miklós Molnár b, Júlia Schönléber a, Ilona Kovalszky c, János Rigó Jr. a (a First
Utero-placental cellular and subcellular expression of opposing AT1R and B2R receptors in normal and preeclamptic pregnancies Gloria Valdes a, Stephanie Acuña a, Gloria X. Soto b (a Escuela Medicina Pontificia Universidad Catolica, Santiago, Chile, b Hospital San Borja Arriarán, Santiago, Chile)
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 53–156
Objectives: The main receptors of the antagonic reninangiotensin and kallikrein–kinin systems, AT1R and B2R, are expressed in villous and extravillous trophoblasts in normal and preeclamptic placentas, and have in vitro and in vivo effects related to placentation. Expecting a functional equilibrium in normal pregnancy and a disruption favouring vasoconstriction in preeclampsia, we studied the cellular/ subcellular localization and balance between AT1R and B2R in normal and preeclamptic pregnancies. Methods: Placentas, obtained from normotensive and preeclamptic pregnancies (n = 14 per group) at the San BorjaArriarán Hospital, were separated into villous zone and basal plate, and submitted to immunohistochemistry, WB and double-labeling immunoelectron microscopy using polyclonal and monoclonal anti-AT1R and B2R. Results: In the placenta of normal and preeclamptic pregnancies AT1R and B2R receptor immunoreactivity was expressed in syncytiotrophoblast and endothelium; the basal plate displayed reactivity for both receptors in extravillous trophoblasts and decidual cells. The protein content of AT1R and B2R (65 y 40 KDa respectively) was demonstrated in both placental zones. Neither the content of AT1R, B2R or the AT1R/B2R ratio differed between both groups. In immunoelectron microscopy AT1R and B2R were present in syncytiotrophoblast, extravillous cytotrophoblasts and decidual cells in the cell membrane, the rough endoplasmic reticulum and predominantly in the nucleus. Conclusions: This study demonstrates that the antagonic receptors AT1R and B2R colocalize in the syncytiotrophoblast, endotelium, extravillous trophoblast and decidual cells. Though a disrupted equilibrium between AT1R and B2R was not observed, the salient observation of their nuclear localization opens a new space of action for angiotensin II, bradykinin and especially for the AT1R agonistic autoantibody, posing the need to dissect their intranuclear functions.Grant Fondecyt 1121161.
135
(Osaka University Graduate School of Medicine, Suita, Japan) Objectives: In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin and that nicotine inhibits interleukin 6 (IL-6) productions which maternal serum stimulates. Methods: Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells (HUVECs) treated with nicotine, and with various combinations of soluble fms-like tyrosine kinase 1, soluble endoglin, and nicotine. Enzyme-linked immunosorbent assay (ELISA) was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor- 1 concentrations in the conditioned media treated with nicotine. HUVECs were incubated with or without 0.5% serum from healthy pregnant women at term and treated with or without nicotine in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. IL-6 concentration and nuclear transcription factor kappa B (NF-kB) activities were determined by ELISA-based method. Results: Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fmslike tyrosine kinase 1 and/or soluble endoglin reduced endothelial functions. Placental growth factor, but not transforming growth factor-1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable. IL-6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-kB activation in endothelial cells. Conclusions: Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia. Disclosures: K. Mimura: None. T. Tomimatsu: None. T. Kimura: None. doi:10.1016/j.preghy.2014.10.276
[271-POS] Disclosures: G. Valdes: None. S. Acuña: None. G.X. Soto: None. doi:10.1016/j.preghy.2014.10.275
[270-POS] A possible therapeutic role of nicotine for preeclampsia Kazuya Mimura, Takuji Tomimatsu, Tadashi Kimura
Glucocerebrosidase expression and activity in human placenta from normotensive and preeclamptic pregnancies Jiska M. Jebbink a, Rolf G. Boot b, Remco Keijser b, Perry D. Moerland b, Jan Aten b, Geertruda J. Veenboer b, Madelon van Wely b, Maarten Buimer b, Emiel Ver Loren van Themaat b, Johannes M. Aerts b, Joris A. van der Post b, Gijs B. Afink b, Carrie Ris-Stalpers b (a Onze Lieve Vrouwe Gasthuis & Academic Medical Center, Amsterdam, Netherlands, b Academic Medical Center, Amsterdam, Netherlands)