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Gestational cholestyramine treatment protects adult offspring of ApoE ‐deficient mice against maternal‐hypercholesterolemia‐induced atherosclerosis

Title: Gestational cholestyramine treatment protects adult offspring of ApoE ‐deficient mice against maternal‐hypercholesterolemia‐induced atherosclerosis
Authors: Habib, Marina; Croyal, Mikael; Kaeffer, Bertrand; Grit, Isabelle, I.; Castellano, Blandine; Gourdel, Mathilde; Le May, Cédric; Thorin, Chantal; Nazih, Hassan; Ouguerram, Khadija
Contributors: Physiopathologie des Adaptations Nutritionnelles (PhAN); Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Centre de Recherche en Nutrition Humaine Ouest (CRNH Ouest); Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Structure fédérative de recherche François Bonamy (Nantes Univ - SFR François Bonamy); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Santé; ITX-lab unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX-lab); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS); Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher); École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Institut Des Substances et Organismes de la Mer - UR 2160 (ISOMER); Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie); Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST); Nantes Université - pôle Sciences et technologie; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie; Nantes Université (Nantes Univ); AlimH department of FrenchNational Research Institute for Agriculture, Food andEnvironment (Inrae); research program EPERSAT byregion Pays de la Loire, France.
Source: ISSN: 1748-1708.
Publisher Information: CCSD; Wiley
Publication Year: 2024
Collection: Université de Nantes: HAL-UNIV-NANTES
Subject Terms: atherosclerosis; cholestyramine; hypercholesterolemia; perinatal; [SDV]Life Sciences [q-bio]
Description: International audience ; Aim: Perinatal hypercholesterolemia exacerbates the development of atherosclerotic plaques in adult offspring. Here, we aimed to study the effect of maternal treatment with cholestyramine, a lipid‐lowering drug, on atherosclerosis development in adult offspring of hypercholesterolemic ApoE‐deficient (ApoE −/− ) mice. Methods: ApoE −/− mice were treated with 3% cholestyramine (CTY) during gestation (G). After weaning, offspring (CTY‐G) were fed control diet until sacrificed at 25weeks of age. Atherosclerosis development in the aortic root of offspring was assessed after oil‐red‐o staining, along with some of predefined atherosclerosis regulators such as LDL and HDL by high‐performance liquid chromatography (HPLC), and bile acids (BA) and trimethylamine N‐oxide (TMAO) by liquid chromatography‐mass spectrometry (LC–MS/MS). Results: In pregnant dams, cholestyramine treatment resulted in significantly lower plasma total‐ and LDL‐cholesterol as well as gallbladder total BA levels. In offspring, both males and females born to treated dams displayed reduced atherosclerotic plaques areas along with less lipid deposition in the aortic root. No significant change in plasma total cholesterol or triglycerides was measured in offspring, but CTY‐G males had increased HDL‐cholesterol and decreased apolipoproteins B100 to A‐I ratio. This latter group also showed reduced gallbladder total and specifically tauro‐conjugated bile acid pools, whereas for CTY‐G females, hydrophilic plasma tauro‐conjugated BA pool was significantly higher. They also benefited from lower plasma TMAO. Conclusion Prenatal cholestyramine treatment reduces atherosclerosis development in adult offspring of ApoE −/− mice along with modulating the plaques' composition as well as some related biomarkers such as HDL‐C, bile acids and TMAO.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/38546340; PUBMED: 38546340; WOS: 001193298500001
DOI: 10.1111/apha.14133
Availability: https://hal.science/hal-04797680; https://hal.science/hal-04797680v1/document; https://hal.science/hal-04797680v1/file/Acta%20Physiologica%20-%202024%20-%20Habib%20-%20Gestational%20cholestyramine%20treatment%20protects%20adult%20offspring%20of%20ApoE%E2%80%90deficient%20mice.pdf; https://doi.org/10.1111/apha.14133
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.E4F0129E
Database: BASE