Combination of dietary phytosterols plus niacin or fenofibrate: effects on lipid profile and atherosclerosis in apo E-KO mice

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• 作者：Yeganeh ; Behzad ; Moshtaghi-Kashanian ; Ghollam-Reza ; DeClercq ; Vanessa ; Moghadasian ; Mohammed H.
• 关键词：Apo E-KO mice ; Atherosclerosis ; Fenofibrate ; Lipoproteins ; Niacin ; Phytosterols
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2005
• 出版时间：April, 2005
• 年：2005
• 卷：16
• 期：4
• 页码：222-228
• 全文大小：1.32 M

文摘

Patients with mixed dyslipidemias (increased LDL cholesterol and triglyceride as well as low HDL cholesterol levels) benefit from a combination of lipid-modifying drugs such as statins, niacin, fibrates and ezetemibe. However, safety, tolerability and cost are a concern in drug combination therapy. Dietary phytosterols reduce LDL cholesterol, and niacin or fenofibrate primarily reduces triglyceride and increases HDL-cholesterol levels. Thus, we hypothesized that a combination of phytosterols with niacin or fenofibrate will synergistically impact lipoprotein profile and atherogenesis in apo E-KO mice. Phytosterols alone significantly reduced plasma total cholesterol levels (14.1 vs. 16.9 mmol/L, P<.05) and the extent of atherosclerosis (0.42 vs. 0.15 mm², P<.05). The addition of fenofibrate to phytosterols increased plasma total cholesterol levels by >50 % (14.1 vs. 21.6 mmol/L, P<.05) and decreased HDL-cholesterol concentrations by 50 % (0.8 vs. 0.4 mmol/L). These changes were accompanied by slight reductions in the extent of atherosclerosis (0.42 vs. 0.34 mm², P>0.05) as compared to controls, suggesting other potential anti-atherogenic effects of fenofibrate. Unlike fenofibrate, niacin caused an increase of 150 % (P<.05) in HDL-cholesterol concentrations and a decrease of 22 % (P<.05) in total cholesterol levels which were associated with significant reductions (65 % , P<.05) in atherosclerotic lesion size as compared to controls. Neither the addition of niacin nor of fenofibrate reduced plasma triglyceride levels. In conclusion, the addition of niacin to phytosterols synergistically increases HDL-cholesterol levels, while a combination of phytosterols and fenofibrate results in no synergistic effects in apo E-KO mice. Further studies in other animal models are needed to establish synergetic effects between these lipid-modifying dietary and pharmacological agents.