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Title:Finasteride lowers cholesterol in humans and delays atherosclerosis progression in Ldlr-/- mice
Author(s):McQueen, James Patrick
Advisor(s):Amengual , Jaume
Contributor(s):Erdman , John; Flaws, Jodi
Department / Program:Nutritional Sciences
Discipline:Nutritional Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:M.S.
Genre:Thesis
Subject(s):cholesterol
atherosclerosis
finasteride
Abstract:Plasma cholesterol and sex hormones are strong risk factors associated with atherosclerosis, the leading cause of death worldwide. The objective of this study was to determine the role of finasteride, a drug that inhibits the activation of testosterone to dihydrotestosterone, on plasma lipid profile and atherogenesis. For our clinical study, we applied regression models to examine associations between circulating lipid profile and finasteride using the National Health and Nutrition Examination Survey database. After controlling for covariates, we observed a significant reduction in total cholesterol levels in subjects taking finasteride. In our preclinical model, we tested the effect of finasteride in atheroprone low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed increasing doses of finasteride for 12 weeks. Finasteride reduced circulating cholesterol levels and resulted in a reduction in lesion size, necrotic core area, and immune cell content. Global transcriptome analysis of liver showed an up-regulation of bile acid biosynthesis and oxidative phosphorylation, accompanied by a reduction in inflammatory markers. Our results show that finasteride is associated with a reduction in plasma cholesterol in both human and mice and highlight the potential role of this drug in the reduction of atherosclerosis.
Issue Date:2021-12-09
Type:Thesis
URI:http://hdl.handle.net/2142/114110
Rights Information:Copyright 2021 James McQueen
Date Available in IDEALS:2022-04-29
Date Deposited:2021-12


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