Dra. Andrea Leiva M.
División de Obstetricia y Ginecología
Laboratorio de Fisiología Celular y Molecular
Contacto
aaleiva@puc.cl
Líneas de Investigación:
La línea de investigación desarrollada desde el año 2011 se centra en el estudio de los efectos de la hipercolesterolemia materna durante el embarazo sobre la función endotelial de la placenta y los mecanismos implicados en el tráfico de colesterol desde la madre al feto en estas condiciones. Hemos determinado que niveles de colesterol materno total y de lipoproteínas de baja densidad elevados por sobre los niveles fisiológicos, alteran la función de la vasculatura de la placenta, lo que eventualmente podría afectar además la vasculatura del niño en desarrollo predisponiéndolo al desarrollo de enfermedades cardiovasculares.
De esta forma, nuestro objetivo es evaluar los efectos de la hipercolesterolemia materna del embarazo sobre:
· La función endotelial feto-placentaria: ruta L-arginina/oxido nítrico.
· La función endotelial feto-placentaria: ruta arginasas/urea.
· La función endotelial feto-placentaria: actividad de la óxido nítrico sintasa.
· Transporte de lipoproteínas desde la madre al feto a través de la placenta.
· Expresión de receptores y transportadores de lipoproteínas y colesterol en la placenta humana.
· Funcionalidad y composición de las lipoproteínas maternas.
· Funcionalidad y composición de las lipoproteínas fetales.
Proyectos de Investigación:
2011 – 2014: Investigador responsable. Proyecto FONDECYT iniciación: «Effect of maternal supraphysiological hypercholesterolemia in pregnancy in the endothelial function and atherosclerosis of the human placenta vasculature».
2013 – 2014: Investigador responsable. Proyecto REDES de CONICYT: «International network for the study of feto-placental vascular dysfunction in diseases of pregnancy»
2014 – 2014: Co-Investigador. Proyecto fondo de apoyo a la organización de reuniones científicas de la Vicerrectoría de Investigacion, PUC. (IR: Luis Sobrevia)
2015 – 2019: Investigador responsable. Proyecto FONDECYT regular: «Involvement of PCSK9 in human maternal supraphysiological hypercholesterolemia. Effects on placental cholesterol traffic and functionality of neonatal lipoproteins».
2015 – 2019: Co-Investigador Proyecto FONDECYT regular: «Role of insulin receptors and adenosine receptors in prevention of fetoplacental endothelial dysfunction by insulin in women with gestational diabetes mellitus» (IR: Luis Sobrevia).
Publicaciones:
· Leiva A; Fuenzalida B, Westermeier F, Toledo F, Salommon C, Gutierrez J, Sanhueza C, Pardo F, Sobrevia L. (2015). Role for tetrahydrobiopterin in the fetoplacental endothelial dysfunction in maternal supraphysiological hypercholesterolemia. Oxidative Medicine and Cellular Longevity. Article ID 451790.
· Westermeier F, Sáez T, Arroyo P, Toledo F, Gutiérrez J, Sanhueza C, Pardo F, Leiva A, Sobrevia L. (2015). Insulin receptor isoforms: an integrated view focused on gestational diabetes mellitus. Diabetes Metab Res Rev. 2015 Oct 2. doi: 10.1002/dmrr.2729.
· Leiva A; Salsoso S; Sáez T; Sanhueza C; Pardo F, Sobrevia L. (2015). Cross-sectional and longitudinal lipid determination studies in pregnant women reveal an association between increased maternal LDL cholesterol concentrations and reduced human umbilical vein relaxation. Placenta. 36:895-902.
· Salsoso R, Guzmán-Gutiérrez E, Sáez T, Bugueño K, Ramírez MA, Farías M, Pardo F, Leiva A, Sanhueza C, Mate A, Vázquez C, Sobrevia L. (2015). Insulin restores L-arginine transport requiring adenosine receptors activation in umbilical vein endothelium from late-onset preeclampsia. Placenta. 36:287-296.
· Sobrevia L, Salsoso R, Sáez T, Sanhueza C, Pardo F, Leiva A. (2015). Insulin therapy and fetoplacental vascular function in gestational diabetes mellitus. Exp Physiol.100 :231-238.
· Pardo F, Silva L, Sáez T, Salsoso R, Gutiérrez J, Sanhueza C, Leiva A, Sobrevia L. (2015). Human supraphysiological gestational weight gain and fetoplacental vascular dysfunction. Int J Obes (Lond). 39:1264-73.
· González M, Rojas S, Avila P, Cabrera L, Villalobos R, Palma C, Aguayo C, Peña E, Gallardo V, Guzmán-Gutiérrez E, Sáez T, Salsoso RSanhueza C, Pardo F, Leiva A, Sobrevia L. (2015). Insulin reverses d-glucose-increased nitric oxide and reactive oxygen species generation in human umbilical vein endothelial cells. Plos One. 10:e0122398.
· Westermeier F, Salomon C, Farias M, Arroyo P, Sáez,T, Salsoso R, Sanhueza C, Guzmán-Gutiérrez E, Pardo F, Leiva, A, Sobrevia L. (2015). Insulin requires normal expression and signalling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium. FASEB J. 29:37-49.
· Salsoso R, Guzmán-Gutiérrez E, Arroyo P, Salomón C, Zambrano S, Ruiz-Armenta MV, Blanca AJ, Pardo F, Leiva A, Mate A, Sobrevia L, Vázquez C. (2014). Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. Plos One 9: e90339.
· Westermeier F, Salomon C, Farias M, Arroyo P, Sáez T, Salsoso R, Sanhueza C, Guzmán-Gutiérre E, Pardo F, Leiva A, Sobrevia L. (2014). Insulin Requires Normal Expression and Signalling of Insulin Receptor A to Reverse Gestational Diabetes-reduced Adenosine Transport in Human Umbilical Vein Endothelium. The FASEB journal. In press
· Guzmán-Gutiérrez E, Arroyo P, Salsoso R, Fuenzalida B, Sáez T, Leiva A, Pardo F, Sobrevia L. (2014). Role of insulin and adenosine in the human placenta microvascular and macrovascular endothelial cell dysfunction in gestational diabetes mellitus. Microcirculation 21: 26-37.
· Guzmán-Gutierrez E, Veas C, Leiva A, Escudero C, Sobrevia L. (2014). Is a low level of free thyroxine in the maternal circulation associated with altered endothelial function in Gestational Diabetes? Front Pharmacol. 5:136. doi: 10.3389/fphar.2014.00136
· Leiva A, de Medina CD, Salsoso R, Sáez T, San Martín S, Abarzúa F, Farías M, Guzmán-Gutiérrez E, Pardo F, Sobrevia L. (2013). Maternal hypercholesterolemia in pregnancy causes placenta endothelial dysfunction: role of eNOS and arginase II. Arterioscler Thromb Vasc Biol. 33 :2244-2253.
· Calligaris S, Lecanda M, Solis F, Ezquer M, Gutiérrez J, Brandan E Leiva A, L Sobrevia L, Conget P. (2013). Mice long-term high-fat diet feeding recapitulates human cardiovascular alterations: an animal model to study the early phases of diabetic cardiomyopathy. Plos One 8 :e60931.
· Pardo F, Arroyo P, Salomón C, Westermeier F, Salsoso R, Sáez T, Guzmán-Gutiérrez E, Leiva A, Sobrevia L. (2013). Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus. Placenta 34:1121-1127.
· Salomón C, Westermeier F, Puebla C , Arroyo P, Guzmán-Gutiérrez E, Pardo F, Leiva A, Sobrevia L. (2012). Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. Plos One 7:e40578.
· Pardo F, Arroyo P, Salomón C, Westermeier F, Guzmán-Gutiérrez E, Leiva A, Sobrevia L. (2012). Gestational diabetes mellitus and the role of adenosine in the human placental endothelium and central nervous system. J Diabetes Metab. S2-S10.
· Guzmán-Gutiérrez E, Westermeier F, Salomón C, Gonzalez M, Pardo F, Leiva A, Sobrevia L. (2012). Insulin-increased L-Arginine transport requires A2A adenosine receptors activation in human umbilical vein endothelium. Plos One 7:e41705.
· Mate A, Vazquez C, Leiva A, Sobrevia L. (2012). New therapeutic approaches to treating hypertension in pregnancy. Drug Discov Today. 17:1307-1315.
· Aravena C, Beltran A, Cornejo M, DIaz E, Torres V, Guzmán-Gutiérrez E, Pardo F, Leiva A, Sobrevia L, Ramirez M. (2012). Potential role of sodium-proton exchangers in the low concentration arsenic trioxide-increased intracellular pH and cell proliferation. Plos One 7: e51451.
· Amigo L, Quiñones V, Leiva A, Busso D, Zanlungo S, Nervi F, Rigotti A. (2011). Apolipoprotein A-I deficiency does not affect biliary lipid secretion and gallstone formation in mice. Liver Int. 31:263-271.
· González M, Gallardo V, Rodríguez N, Salomón C, Westermeier F, Guzmán-Gutiérrez E, Abarzúa F, Leiva A, Casanello P, Sobrevia L. (2011). Insulin-stimulated L-arginine transport requires SLC7A1 gene expression and is associated with human umbilical vein relaxation. J Cell Physiol. 226:2916-2924.
· Westermeier F, Salomón C, González M, Puebla C, Guzmán-Gutiérrez E, Cifuentes F, Leiva A, Casanello P, Sobrevia L. (2011). Insulin restores gestational diabetes mellitus-reduced adenosine transport involving differential expression of insulin receptor isoforms in human umbilical vein endothelium. Diabetes 60 :1677-1687.
· Leiva A, Verdejo H, Benítez ML, Martínez A, Busso D, Rigotti A. (2011). Mechanisms regulating hepatic SR-BI expression and their impact on HDL metabolism. Atherosclerosis 217 :299-307.
· Guzmán-Gutiérrez E, Abarzúa F, Belmar C, Nien JK, Ramírez MA, Arroyo P, Salomón C, Westermeier F, Puebla C, Leiva A, Casanello P, Sobrevia L. (2011). Functional link between adenosine and insulin: a hypothesis for fetoplacental vascular endothelial dysfunction in gestational diabetes. Curr Vasc Pharmacol. 9:750-762.
· Leiva A, Pardo F, Ramírez MA, Farías M, Casanello P, Sobrevia L. (2011). Fetoplacental vascular endothelial dysfunction as an early phenomenon in the programming of human adult diseases in subjects born from gestational diabetes mellitus or obesity in pregnancy. Exp Diabetes Res. 2011:349286
· Sobrevia L, Abarzúa F, Nien JK, Salomón C, Westermeier F, Puebla C, Cifuentes F, Guzmán-Gutiérrez E, Leiva A, Casanello P. (2011). Differential placental macrovascular and microvascular endothelial dysfunction in gestational diabetes. Placenta 32:S159-S164.
Libros y patentes (Últimos 10 años):
· Lappas M, Leiva A, Pardo F, Sobrevia L, Jawerbaum A. (2014). Oxidative stress in pregnancies complicated by diabetes in Gestational diabetes and oxidative stress. Eds. Lappas M. Springer Science+Business Media. New York. Chapter 3,47-79.
· Sobrevia L, Sáez T, Fuenzalida B, Salsoso R, Vázquez MC, Arroyo P, Guzmán-Gutiérrez E, Pardo F, Leiva A. (2014). Transplacental transport of calcium in health and disease in Calcium and vitamin D DANONE South Cone. Eds. Uauy R, Carmuega E and Weil R.Ed. Lenguamadre, Argentina. Chapter 8 :103-134.
· Leiva A, Diez de Medina C, Guzmán-Gutiérrez E, Pardo F, Sobrevia L. (2013). Maternal Hypercholesterolemia in Gestational Diabetes and the Association with Placental Endothelial Dysfunction. En: Gestational Diabetes -Causes, Diagnosis and Treatment. Ed. In Tech, Croatia. Chapter 6: 103-134.
· Guzmán-Gutiérrez E, Arroyo P, Pardo F, Leiva A, Sobrevia L. (2013). The Adenosine–Insulin Signaling Axis in the Fetoplacental Endothelial Dysfunction in Gestational Diabetes. En: Gestational Diabetes – Causes, Diagnosis and Treatment. Ed. In Tech, Croatia. Chapter 4: 49-78.
· Sobrevia L, Guzmán-Gutiérrez E, Westermeier F, Salomón C, Arroyo P, Palacios E, Bugueño K, Santos M, Diez de Medina C, González M, Escudero C, Mate A, Vásquez CM, Pardo F, Leiva A. (2012). Fetoplacental vascular pathophysiology in preeclampsia. En: Recent Research Development in Physiology. Ed. Research Signpost, India. Vol 5, chapter 7: 105-158.
· González M, Muñoz E, Puebla P, Guzmán-Gutiérrez E, Cifuentes F, Nien JK, Abarzúa F, Leiva A, Casanello P, Sobrevia L. (2011). Maternal and fetal metabolic dysfunction in pregnancy diseases associated with vascular oxidative and nitrative stress. En: The Molecular Basis for the Link between Maternal Health and the origin of Fetal Congenital Abnormalities An Overview of Association with Oxidative Stress. Ed. Bentham Science Publishers, USA. Chapter 8: 98-115.