Gestational cholestyramine treatment protects adult offspring of ApoE ‐deficient mice against maternal‐hypercholesterolemia‐induced atherosclerosis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Acta Physiologica Année : 2024

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

Marina Habib
Mikael Croyal
  • Fonction : Auteur
Isabelle Grit
  • Fonction : Auteur
Mathilde Gourdel
  • Fonction : Auteur
Blandine Castellano
  • Fonction : Auteur
Cédric Le May
  • Fonction : Auteur
Chantal Thorin
  • Fonction : Auteur
Hassan Nazih
  • Fonction : Auteur
Khadija Ouguerram
  • Fonction : Auteur

Résumé

Abstract 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.

Dates et versions

hal-04525933 , version 1 (29-03-2024)

Identifiants

Citer

Marina Habib, Mikael Croyal, Bertrand Kaeffer, Isabelle Grit, Mathilde Gourdel, et al.. Gestational cholestyramine treatment protects adult offspring of ApoE ‐deficient mice against maternal‐hypercholesterolemia‐induced atherosclerosis. Acta Physiologica, 2024, ⟨10.1111/apha.14133⟩. ⟨hal-04525933⟩

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