Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia

Maternal physiological hypercholesterolemia (MPH) occurs during pregnancy to assure fetal development. Some pregnant women develop maternal supraphysiological hypercholesterolemia (MSPH) characterized by increased levels of low-density lipoprotein (LDL). We aim to determine if proprotein convertase...

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Main Authors: Claudette Cantin, María Jesús Garchitorena, Rodrigo Escalona, Jorge A. Carvajal, Sebastián E. Illanes, Jaime Gutierrez, Andrea Leiva
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/5/869
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author Claudette Cantin
María Jesús Garchitorena
Rodrigo Escalona
Jorge A. Carvajal
Sebastián E. Illanes
Jaime Gutierrez
Andrea Leiva
author_facet Claudette Cantin
María Jesús Garchitorena
Rodrigo Escalona
Jorge A. Carvajal
Sebastián E. Illanes
Jaime Gutierrez
Andrea Leiva
author_sort Claudette Cantin
collection DOAJ
description Maternal physiological hypercholesterolemia (MPH) occurs during pregnancy to assure fetal development. Some pregnant women develop maternal supraphysiological hypercholesterolemia (MSPH) characterized by increased levels of low-density lipoprotein (LDL). We aim to determine if proprotein convertase subtilisin/kexin type 9 (PCSK9) levels (a protein that regulate the availability of LDL receptor in the cells surface), as well as the composition and function of LDL, are modulated in MSPH women. This study included 122 pregnant women. Maternal total cholesterol (TC), LDL, triglycerides and PCSK9 increased from first (T1) to third trimester (T3) in MPH women. At T3, maternal TC, LDL, PCSK9 and placental abundances of PCSK9 were significantly higher in MPSH compared to MPH. Circulating PCSK9 levels were correlated with LDL at T3. In MSPH women, the levels of lipid peroxidation and oxidized LDL were significantly higher compared to MPH. LDL isolated from MSPH women presented significantly higher triglycerides and ApoB but lower levels of ApoAI compared to MPH. The formation of conjugated dienes was earlier in LDL from MSPH and in endothelial cells incubated with these LDLs; the levels of reactive oxygen species were significantly higher compared to LDL from MPH. We conclude that increased maternal PCSK9 would contribute to the maternal elevated levels of pro-atherogenic LDL in MSPH, which could eventually be related to maternal vascular dysfunction.
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spelling doaj.art-6746918f0f7642dfad54dbd6c6812c7a2023-11-23T09:50:59ZengMDPI AGAntioxidants2076-39212022-04-0111586910.3390/antiox11050869Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological HypercholesterolemiaClaudette Cantin0María Jesús Garchitorena1Rodrigo Escalona2Jorge A. Carvajal3Sebastián E. Illanes4Jaime Gutierrez5Andrea Leiva6School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileSchool of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileSchool of Medical Technology, Faculty of Medicine and Sciences, Universidad San Sebastián, Santiago 7510157, ChileSchool of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileFaculty of Medicine, Universidad de los Andes, Santiago 7550000, ChileSchool of Medical Technology, Faculty of Medicine and Sciences, Universidad San Sebastián, Santiago 7510157, ChileSchool of Medical Technology, Faculty of Medicine and Sciences, Universidad San Sebastián, Santiago 7510157, ChileMaternal physiological hypercholesterolemia (MPH) occurs during pregnancy to assure fetal development. Some pregnant women develop maternal supraphysiological hypercholesterolemia (MSPH) characterized by increased levels of low-density lipoprotein (LDL). We aim to determine if proprotein convertase subtilisin/kexin type 9 (PCSK9) levels (a protein that regulate the availability of LDL receptor in the cells surface), as well as the composition and function of LDL, are modulated in MSPH women. This study included 122 pregnant women. Maternal total cholesterol (TC), LDL, triglycerides and PCSK9 increased from first (T1) to third trimester (T3) in MPH women. At T3, maternal TC, LDL, PCSK9 and placental abundances of PCSK9 were significantly higher in MPSH compared to MPH. Circulating PCSK9 levels were correlated with LDL at T3. In MSPH women, the levels of lipid peroxidation and oxidized LDL were significantly higher compared to MPH. LDL isolated from MSPH women presented significantly higher triglycerides and ApoB but lower levels of ApoAI compared to MPH. The formation of conjugated dienes was earlier in LDL from MSPH and in endothelial cells incubated with these LDLs; the levels of reactive oxygen species were significantly higher compared to LDL from MPH. We conclude that increased maternal PCSK9 would contribute to the maternal elevated levels of pro-atherogenic LDL in MSPH, which could eventually be related to maternal vascular dysfunction.https://www.mdpi.com/2076-3921/11/5/869pregnancylow-density lipoproteinsPCSK9atherogenic profile
spellingShingle Claudette Cantin
María Jesús Garchitorena
Rodrigo Escalona
Jorge A. Carvajal
Sebastián E. Illanes
Jaime Gutierrez
Andrea Leiva
Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia
Antioxidants
pregnancy
low-density lipoproteins
PCSK9
atherogenic profile
title Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia
title_full Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia
title_fullStr Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia
title_full_unstemmed Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia
title_short Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia
title_sort increased circulating levels of pcsk9 and pro atherogenic lipoprotein profile in pregnant women with maternal supraphysiological hypercholesterolemia
topic pregnancy
low-density lipoproteins
PCSK9
atherogenic profile
url https://www.mdpi.com/2076-3921/11/5/869
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