title: Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia.
abstract: Maternal physiological hypercholesterolemia occurs during pregnancy, ensuring normal fetal development. In some cases, the maternal plasma cholesterol level increases to above this physiological range, leading to maternal supraphysiological hypercholesterolemia (MSPH). This condition results in endothelial dysfunction and atherosclerosis in the fetal and placental vasculature. The fetal and placental endothelial dysfunction is related to alterations in the L-arginine/nitric oxide (NO) pathway and the arginase/urea pathway and results in reduced NO production. The level of tetrahydrobiopterin (BH4), a cofactor for endothelial NO synthase (eNOS), is reduced in nonpregnant women who have hypercholesterolemia, which favors the generation of the superoxide anion rather than NO (from eNOS), causing endothelial dysfunction. However, it is unknown whether MSPH is associated with changes in the level or metabolism of BH4; as a result, eNOS function is not well understood. This review summarizes the available information on the potential link between MSPH and BH4 in causing human fetoplacental vascular endothelial dysfunction, which may be crucial for understanding the deleterious effects of MSPH on fetal growth and development.
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Fuenzalida
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Faculty of Chemical & Pharmaceutical Sciences and Faculty of Medicine, Universidad de Chile, 8380492 Santiago, Chile ; Faculty of Science, Universidad San Sebastián, 7510157 Santiago, Chile.
authors.forename: Francisco
authors.identifier: 0000-0002-4476-4198
authors.initials: F
authors.lastname: Westermeier
authors.affiliation: Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, 3780000 Chillán, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Toledo
authors.affiliation: University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Australia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Salomón
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile ; Cellular Signaling and Differentiation Laboratory (CSDL), Health Sciences Faculty, Universidad San Sebastian, 7510157 Santiago, Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: Gutiérrez
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sanhueza
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile.
authors.forename: Fabián
authors.initials: F
authors.lastname: Pardo
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile ; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Australia ; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain.
authors.forename: Luis
authors.identifier: 0000-0001-5802-2243
authors.initials: L
authors.lastname: Sobrevia
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D001894:Borohydrides / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011247:Pregnancy
chemical_list: D001894:Borohydrides; D001708:Biopterins; D009569:Nitric Oxide; D001120:Arginine; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin