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

Autor: Habib M; UMR1280 Pathophysiology of Nutritional Adaptations, Nantes Université, INRAE, Nantes, France., Croyal M; Mass Spectrometry Core Facility, CRNH-Ouest, Nantes, France.; Institut du thorax, Nantes Université, CNRS, INSERM, Nantes, France.; UMS 016, UMS 3556, Nantes Université, Inserm, CNRS, Nantes, France., Kaeffer B; UMR1280 Pathophysiology of Nutritional Adaptations, Nantes Université, INRAE, Nantes, France., Grit I; UMR1280 Pathophysiology of Nutritional Adaptations, Nantes Université, INRAE, Nantes, France., Castellano B; UMR1280 Pathophysiology of Nutritional Adaptations, Nantes Université, INRAE, Nantes, France., Gourdel M; Institut du thorax, Nantes Université, CNRS, INSERM, Nantes, France., Le May C; UMS 016, UMS 3556, Nantes Université, Inserm, CNRS, Nantes, France., Thorin C; UMR0703 PAnTher, École Nationale Vétérinaire, Agroalimentaire et de l'Alimentation, Nantes, France., Nazih H; UR2160 ISOMer, Nantes Université, Nantes, France., Ouguerram K; UMR1280 Pathophysiology of Nutritional Adaptations, Nantes Université, INRAE, Nantes, France.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2024 May; Vol. 240 (5), pp. e14133. Date of Electronic Publication: 2024 Mar 28.
DOI: 10.1111/apha.14133
Abstrakt: 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.
(© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
Databáze: MEDLINE
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