MARA SANDRA HOSHIDA
Projetos de Pesquisa
Unidades Organizacionais
LIM/57 - Laboratório de Fisiologia Obstétrica, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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conferenceObject Longitudinal serum levels of Placental Growth Factor and sFlt-1 throughout gestation in normotensive pregnancies and those complicated by hypertensive disorders(2013) COSTA, R. A.; HOSHIDA, M. S.; ALVES, E. A.; V, R. P. Francisco; ZUGAIB, M.Background: Preeclampsia (PE) prevalence is higher in women with chronic hypertension (CH). Predictive markers for PE in this group could be particularly important. We aimed to evaluate serum levels of PlGF and sFlt-1 throughout pregnancies complicated by isolated PE, CH and PE superimposed on CH (PE+CH) compared to normotensive (NT) pregnancies. Methods: Peripheral blood samples have been collected from NT and CH pregnancies at gestational ages of 20, 26, 32 and 36 weeks and stored to be assayed by ELISA. This study was approved by local Ethics Committee. To date, samples have been partially assayed. Results: Levels of sFlt-1 increased throughout pregnancy in all groups. Levels of PlGF increased until 32 weeks in pregnancies not complicated by PE (NT and CH) and until 26 weeks in those complicated by PE (PE and PE+HC), thereafter PlGF levels decreased in all groups. Conclusions: preliminary data, still too short for statistical testing.- EFFECT OF THE MICROENVIRONMENT ON THE PLACENTAL BEHAVIOUR: RESPONSE OF THE CHORIONIC VILLI TO NORMAL AND PREECLAMPTIC PREGNANT SERUM(2017) PRADO, Karen; CASTRO, Karla; LORENZON-OJEA, Aline; CARDOSO, Elaine; HOSHIDA, Mara; ALVES, Eliane; FRANCISCO, Rossana P. Vieira; ZUGAIB, Marcelo; BEVILACQUAL, Estela
- The Impact of Immunosuppressive Drugs on Human Placental Explants(2019) GOMES, Sara Z.; ARAUJO, Franciele; BANDEIRA, Carla L.; OLIVEIRA, Leandro G.; HOSHIDA, Mara S.; ZUGAIB, Marcelo; FRANCISCO, Rossana P. V.; BEVILACQUA, EstelaThe use of immunosuppressive drugs guarantees the vitality of the graft and allows gestation in spite of intercurrences such as prematurity and intrauterine growth restriction. However, little is known about the direct effects of immunosuppressive drugs on placental cells. We investigated the effects of immunosuppressive drugs in the chorionic villous explants from human term placentas of healthy gestations. Human placental explants from term gestations (37-39 week gestational age, n = 12) were exposed to cyclosporine A (CSA, 0, 62.5, 125, 1250 ng/mL) or azathioprine (AZA, 0, 5, 10, 100 ng/mL) separately or, in combination for up to 48 hours. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed a significant decrease in the explant metabolic activity between AZA and the control group (24 hours, 100 ng/mL, 48 hours, all concentrations, P < .005). Cyclosporin A (CsA) reduced cell activity when associated with AZA (48 hours, P < .005). Fibrinoid deposits increased in AZA-treated explants alone (5 ng/mL, 48 hours; 10 ng/mL, 24-48 hours; P < .005) or when associated with CsA (10 AZA/125 CsA, P < .05), whereas in CsA treatment alone, there was an augment in syncytial knots (24-48 hours, P < .005). The sFLT1 gene (24 hours, P < .05) and protein (P < .005) expression increased in AZA and CsA-treatments separately or in combination (P < .05). Placental growth factor increased in AZA (24 hours, 10 ng/mL) and CsA (125 ng/mL; P < .05). In conclusion, our data indicate that AZA primarily acts on the villous metabolism, perturbing placental homeostasis. Since these drugs may alter the balance of angiogenic factors in its selection for clinical application, their impact on the behavior of placental villous should be considered.
- Expression of dNK cells and their cytokines in twin pregnancies with preeclampsia(2019) AGRA, Isabela K. R.; LIAO, Adolfo W.; HOSHIDA, Mara S.; SCHULTZ, Regina; TOSCANO, Marcello P.; FRANCISCO, Rossana Pv; ZUGAIB, Marcelo; BRIZOT, Maria L.OBJECTIVES: To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia. METHODS: This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins. RESULTS: Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 (p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024). CONCLUSION: A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.
- SERUM OF PATIENTS WITH PREECLAMPSIA ACTIVATES UPR-PERK PATHWAY IN HUMAN TROPHOBLAST CELL LINE HTR8/SVNEO(2019) CASTRO, Karla; PRADO, Karen; LORENZON-OJEA, Aline; FRANCISCO, Rossana; ZUGAIB, Marcelo; HOSHIDA, Mara; ALVES, Eliane; VERAS, Mariana; BEVILACQUA, Estela
- Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells(2022) CASTRO, Karla R.; PRADO, Karen M.; LORENZON, Aline R.; HOSHIDA, Mara S.; ALVES, Eliane A.; FRANCISCO, Rossana P. V.; ZUGAIB, Marcelo; MARQUES, Aldilane L. X.; SILVA, Elaine C. O.; FONSECA, Eduardo J. S.; BORBELY, Alexandre U.; VERAS, Mariana M.; BEVILACQUA, EstelaPreeclampsia (PE) is a hypertensive disease of pregnancy-associated with placental cell death and endoplasmic reticulum (ER) stress. It is unknown whether systemic factors aggravate placental dysfunction. We investigated whether serum factors in pregnant women with PE activate ER stress and unfolded protein responses (UPRs) in placental explants and trophoblast cells lineage. We cultured placental explants from third-trimester term placentas from control non-preeclamptic (NPE) pregnant women with serum from women with PE or controls (NPE). In PE-treated explants, there was a significant increase in gene expression of GADD34, CHOP, and SDF2. At the protein level, GRP78, SDF2, p-eIF2 alpha, and p-eIF2 alpha/eIF2 alpha ratio were also augmented in treated explants. Assays were also performed in HTR8/SV-neo trophoblast cell line to characterize the putative participation of trophoblast cells. In PE serum-treated protein levels of p-eIF2a and the ratio p-elF2 alpha/elF2 alpha increased after 12 h of treatment, while the gene expression of GADD34, ATF4, and CHOP was greater than control. Increased expression of SDF2 was also detected after 24 h-cultured HTR8/SV-neo cells. PE serum increased sFLT1 gene expression and decreased PlGF gene expression in placental explants. Morphologically, PE serum increased the number of syncytial knots and reduced placental cell metabolism and viability. Analysis of the serum of pregnant women with PE through Raman spectroscopy showed changes in amino acids, carotenoids, lipids, and DNA/RNA, which may be associated with the induction of ER stress found in chorionic villi treated with this serum. In conclusion, this study provides evidence that the serum of pregnant women with PE may impact placental villi changing its morphology, viability, and secreted functional factors while triggers ER stress and an UPR. The differences between PE and control sera include molecules acting as inducing factors in these processes. In summary, the results obtained in our assays suggest that after the development of PE, the serum profile of pregnant women may be an additional factor that feeds a continuous imbalance of placental homeostasis. In addition, this study may expand the possibilities for understanding the pathogenesis of this disorder.
conferenceObject Effect of BPP-10c in angiogenic factor expression at the placental villous in preeclampsia(2013) HOSHIDA, M. S.; COSTA, R. A.; BEVILACQUA, E.; V, R. P. Francisco; ZUGAIB, M.Background: BPP-10c is the snake proline-rich oligopeptides, known as bradykinin-potentiating peptide found in Bothrops jararaca. This decapeptide leads to argininosuccinate synthetase activation, consequently sustaining increased nitric oxide production, a critical endogenous molecule to reduce the arterial blood pressure. Angiogenic factor is implicated in the pathogenesis of preeclampsia. We aimed to analyze the effects of BPP-10c in gene expression of angiogenic factor in human chorionic villi explant. Methods: Placentae were collected at delivery from normotensive (NP) and preeclamptic pregnancies (PE). Placental villous explant were cultivated by 24 h with BPP-10c. RNA was extracted and VEGF, PlGF, VEGFR1 and VEGFR2 expression were analyzed by RT-PCR. Results: Compared to expression from NP, PlGF was reduced in PE and VEGF and its receptor were increased in PE. Villous explants BPP-10c-treated from PE exhibited expression of PlGF higher than NP. Discussion: These preliminary results suggest that the BPP-10c could be related with increased angiogenic factor involved in pathophysiology of PE.- EXPRESSION OF ENDOPLASMIC RETICULUM STRESS MARKERS IN CHORIONIC VILLI TREATED WITH SERUM FROM PATIENTS WITH PRE-ECLAMPSIA(2017) CASTRO, Karla; PRADO, Karen; LORENZON-OJEA, Aline; SMUZCEK, Basilio; HOSHIDA, Mara; FRANCISCO, Rossana; ZUGAIB, Marcelo; ALVES, Eliane; VERAS, Mariana; BEVILACQUA, Estela
- Preeclampsia and superimposed preeclampsia: The same disease? The role of angiogenic biomarkers(2016) COSTA, Rafaela A.; HOSHIDA, Mara S.; ALVES, Eliane A.; ZUGAIB, Marcelo; FRANCISCO, Rossana P. V.Objective: We aimed to compare sFlt-1 and placental growth factor (PlGF) levels and the sFlt-1/PlGF ratio between women with preeclampsia and superimposed preeclampsia to, respectively, normotensive and chronic hypertensive ones. Study design: We performed a prospective two-armed cohort in a tertiary teaching hospital in Sao Paulo, Brazil, including 37 normotensive and 60 chronic hypertensive pregnant women. We assessed the serum levels of sFlt-1 and PlGF at 20, 26, 32, and 36 gestational weeks by enzyme-linked immunosorbent assay. Main outcome measures: Having preeclampsia and superimposed preeclampsia. Results: Among normotensive and chronic hypertensive pregnancies, 4 (10.8%) and 14 (23.3%) women developed preeclampsia and superimposed preeclampsia, respectively. Compared with those who remained normotensive, the preeclampsia women presented higher sFlt-1 levels at 32 gestational weeks (4323.45 pg/mL vs. 2242.04 pg/mL, p = 0.019), lower PlGF levels at 20 (183.54 pg/mL vs. 337.38 pg/mL, p = 0.034), 32 (169.69 pg/mL vs. 792.53 pg/mL, p = 0.001), and 36 gestational weeks (252.99 pg/mL vs. 561.81 pg/mL, p = 0.029), and higher sFlt-1/PlGF ratios at 26 (9.02 vs. 1.84, p = 0.004), 32 (23.61 vs. 2.55, p = 0.001), and 36 gestational weeks (49.02 vs. 7.34, p = 0.029). On the other hand, compared with those who remained chronic hypertensive, the superimposed preeclampsia women only presented a higher sFlt-1/PlGF ratio at 32 gestational weeks (9.98 vs. 2.51, p = 0.039). Conclusion: Although angiogenic imbalance is clearly related to preeclampsia, it seems to play a more modest role in superimposed preeclampsia, in which other mechanisms should also be investigated.