Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice |
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Authors: | Shelly Lorraine Royer Lori Sand Thomas Jensen Heather Luo Yi |
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Institution: | Department of Cardiovascular, Metabolic, & Endocrine Diseases, Pfizer Global Research Division, Pfizer, Inc., Groton, CT 06340, USA. |
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Abstract: | Phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids from triglyceride-rich lipoproteins into HDL. PLTP has been shown to be an important factor in lipoprotein metabolism and atherogenesis. Here, we report that chronic high-fat, high-cholesterol diet feeding markedly increased plasma cholesterol levels in C57BL/6 mice. PLTP deficiency attenuated diet-induced hypercholesterolemia by dramatically reducing apolipoprotein E-rich lipoproteins (-88%) and, to a lesser extent, LDL (-40%) and HDL (-35%). Increased biliary cholesterol secretion, indicated by increased hepatic ABCG5/ABCG8 gene expression, and decreased intestinal cholesterol absorption may contribute to the lower plasma cholesterol in PLTP-deficient mice. The expression of proinflammatory genes (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) is reduced in aorta of PLTP knockout mice compared with wild-type mice fed either a chow or a high-cholesterol diet. Furthermore, plasma interleukin-6 levels are significantly lower in PLTP-deficient mice, indicating reduced systemic inflammation. These data suggest that PLTP appears to play a proatherogenic role in diet-induced hyperlipidemic mice. |
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Keywords: | ATP binding cassette transporter G5 ATP binding cassette transporter G8 cholesterol absorption |
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