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Here, we aimed to study the effect of maternal treatment with cholestyramine, a lipid\u2010lowering drug, on atherosclerosis development in adult offspring of hypercholesterolemic ApoE\u2010deficient (ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice were treated with 3% cholestyramine (CTY) during gestation (G). After weaning, offspring (CTY\u2010G) were fed control diet until sacrificed at 25weeks of age. Atherosclerosis development in the aortic root of offspring was assessed after oil\u2010red\u2010o staining, along with some of predefined atherosclerosis regulators such as LDL and HDL by high\u2010performance liquid chromatography (HPLC), and bile acids (BA) and trimethylamine N\u2010oxide (TMAO) by liquid chromatography\u2010mass spectrometry (LC\u2013MS\/MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In pregnant dams, cholestyramine treatment resulted in significantly lower plasma total\u2010 and LDL\u2010cholesterol 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\u2010G males had increased HDL\u2010cholesterol and decreased apolipoproteins B100 to A\u2010I ratio. This latter group also showed reduced gallbladder total and specifically tauro\u2010conjugated bile acid pools, whereas for CTY\u2010G females, hydrophilic plasma tauro\u2010conjugated BA pool was significantly higher. They also benefited from lower plasma TMAO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Prenatal cholestyramine treatment reduces atherosclerosis development in adult offspring of ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice along with modulating the plaques' composition as well as some related biomarkers such as HDL\u2010C, bile acids and TMAO.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14133","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T13:34:44Z","timestamp":1711632884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gestational cholestyramine treatment protects adult offspring of <scp>ApoE<\/scp>\u2010deficient mice against maternal\u2010hypercholesterolemia\u2010induced 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