Browsing by Author "Carvajal, Lorena"

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    Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels
    (2017) Leiva Mendoza, Andrea Alejandra; Guzmán Gutiérrez, Enrique; Contreras Duarte, Susana de las Mercedes; Fuenzalida Saavedra, Bárbara; Cantin, Claudette; Carvajal, Lorena; Salsoso Rodríguez, M. Rocío; Gutiérrez, Jaime; Pardo, Fabián; Sobrevía Luarte, Luis Alberto
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    Cholesterol uptake and efflux are impaired in human trophoblast cells from pregnancies with maternal supraphysiological hypercholesterolemia
    (2020) Fuenzalida, Barbara; Cantin, Claudette; Kallol, Sampada; Carvajal, Lorena; Pasten, Valentina; Contreras-Duarte, Susana; Albrecht, Christiane; Gutierrez, Jaime; Leiva, Andrea
    Maternal physiological (MPH) or supraphysiological hypercholesterolaemia (MSPH) occurs during pregnancy. Cholesterol trafficking from maternal to foetal circulation requires the uptake of maternal LDL and HDL by syncytiotrophoblast and cholesterol efflux from this multinucleated tissue to ApoA-I and HDL. We aimed to determine the effects of MSPH on placental cholesterol trafficking. Placental tissue and primary human trophoblast (PHT) were isolated from pregnant women with total cholesterol <280 md/dL (MPH, n = 27) or >= 280 md/dL (MSPH, n = 28). The lipid profile in umbilical cord blood from MPH and MSPH neonates was similar. The abundance of LDL receptor (LDLR) and HDL receptor (SR-BI) was comparable between MSPH and MPH placentas. However, LDLR was localized mainly in the syncytiotrophoblast surface and was associated with reduced placental levels of its ligand ApoB. In PHT from MSPH, the uptake of LDL and HDL was lower compared to MPH, without changes in LDLR and reduced levels of SR-BI. Regarding cholesterol efflux, in MSPH placentas, the abundance of cholesterol transporter ABCA1 was increased, while ABCG1 and SR-BI were reduced. In PHT from MSPH, the cholesterol efflux to ApoA-I was increased and to HDL was reduced, along with reduced levels of ABCG1, compared to MPH. Inhibition of SR-BI did not change cholesterol efflux in PHT. The TC content in PHT was comparable in MPH and MSPH cells. However, free cholesterol was increased in MSPH cells. We conclude that MSPH alters the trafficking and content of cholesterol in placental trophoblasts, which could be associated with changes in the placenta-mediated maternal-to-foetal cholesterol trafficking.
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    Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women's Weight: Possible Impact on Feto-Placental Vascular Function
    (2020) Contreras-Duarte, Susana; Carvajal, Lorena; Jesus Garchitorena, Maria; Subiabre, Mario; Fuenzalida, Barbara; Cantin, Claudette; Farias, Marcelo; Leiva, Andrea
    Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.
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    Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature
    (2018) Fuenzalida Saavedra, Bárbara; Sobrevia, Bastián; Cantin, Claudette; Carvajal, Lorena; Salsoso Rodríguez, M. Rocío; Gutiérrez, Jaime; Contreras Duarte, Susana de las Mercedes; Sobrevía Luarte, Luis Alberto; Leiva Mendoza, Andrea Alejandra
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    Small extracellular vesicles from pregnant women with maternal supraphysiological hypercholesterolemia impair endothelial cell function in vitro
    (2023) Contreras-Duarte, Susana; Escalona-Rivano, Rodrigo; Cantin, Claudette; Valdivia, Pascuala; Zapata, David; Carvajal, Lorena; Brito, Roberto; Cerda, Alvaro; Illanes, Sebastian; Gutierrez, Jaime; Leiva, Andrea
    Maternal physiological hypercholesterolemia MPH, maternal total cholesterol (TC) levels at term of pregnancy <280 mg/dL) occurs to assure fetal development. Maternal supraphysiological hypercholesterolemia (MSPH, TC levels >280 mg/dL) is a pathological condition associated with maternal, placental, and fetal endothelial dysfunction and early neonatal atherosclerosis development. Small extracellular vesicles (sEVs) are delivered to the extracellular space by different cells, where they modulate cell functions by transporting active signaling molecules, including proteins and miRNA.Aim: To determine whether sEVs from MSPH women could alter the function of endothelial cells (angiogenesis, endothelial activation and nitric oxide synthesis capacity).Methods: This study included 24 Chilean women (12 MPH and 12 MSPH). sEVs were isolated from maternal plasma and characterized by sEV markers (CD9, Alix and HSP70), nanoparticle tracking analysis, transmission electron microscopy, and protein and cholesterol content. The endothelial cell line HMEC-1 was used to determine the uptake of labeled sEVs and the effects of sEVs on cell viability, endothelial tube formation, endothelial cell activation, and endothelial nitric oxide expression and function.Results: In MSPH women, the plasma concentration of sEVs was increased compared to that in MPH women. MSPH-sEVs were highly taken up by HMEC-1 cells and reduced angiogenic capacity and the expression and activity of eNOS without changing cell viability or endothelial activation compared to MPH-sEVs. Conclusion: sEVs from MSPH women impair angiogenesis and nitric oxide synthesis in endothelial cells, which could contribute to MSPH-associated endothelial dysfunction.
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    The autophagy process and oxidized LDL independently modulate the invasion and differentiation of extravillous trophoblastic cells to an endothelial-like phenotype in normoxia
    (2024) Carvajal, Lorena; Escalona, Rodrigo; Rivera, Patricia; Aguilera-Olguin, Macarena; Hernandez-Caceres, Maria Paz; Gutierrez, Jaime; Morselli, Eugenia; Leiva, Andrea
    Introduction: The mechanisms leading to proper placentation are not fully understood. Extravillous trophoblasts (EVTs) are crucial for placentation through invasion and vascular remodeling, which, when impaired, promote a poor placentation. How autophagy could regulate EVTs function and the study of regulators of these processes, such as oxidized low-density lipoproteins (ox-LDL), could contribute to better understand events associated with pregnancy complications related to abnormal placental development, such as preeclampsia (PE). Aim: To investigate the role of autophagy and oxidized LDL (ox-LDL) in invasion and endothelial-like phenotype acquisition of a model of EVTs, as well as to determine the levels of autophagy flux markers in control and PE placentas. Methods: Invasion and endothelial-like phenotype acquisition assays were performed in a cell line model of first trimester EVTs: HTR-8/SVneo cultured in normoxia (oxygen concentration of 20 %), in the absence or the presence of the autophagy inhibitor bafilomycin or/and ox-LDL. Markers of autophagic flux were evaluated in human term placentas. Results: Autophagy is essential for EVTs to acquire an endothelial-like phenotype but does not affect invasion. Conversely, ox-LDL decreases invasion and reticular structures formation, independent of autophagy. At pregnancy term, the levels of the autophagy markers LC3 and p62 are deregulated in the trophoblast cells of PE placentas. Conclusion: Autophagy is necessary for proper endothelial-like phenotype acquisition in HTR-8/SVneo cultured in normoxia, and ox-LDL impairs this process as well as the invasion of EVTs by a mechanism independent of autophagy. Changes in autophagy and/or in the concentration of ox-LDL could affect placental vascular remodeling.