Submitted on July 25, 2007
Revised on January 4, 2008
Accepted on January 14, 2008
Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice
Lorraine Shelly, Lori Royer, Thomas Sand, Heather Jensen, and Yi Luo
Cardiovascular and Metabolic Diseases, Pfizer Inc, Groton, CT 06340
Corresponding Author: yi.luo{at}pfizer.com
Phospholipid transfer protein (PLTP) facilitates transfer of phospholipids from triglyceride-rich lipoproteins (TRL) 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 elevated plasma cholesterol levels in C57BL/6 mice. PLTP deficiency attenuated diet-induced hypercholesterolemia by dramatically reducing ApoE-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 pro-inflammatory genes (ICAM-1 and VCAM-1) is reduced in aorta of PLTP knockout mice compared to wild type mice fed with either a chow or high cholesterol diet. Furthermore, plasma IL-6 levels are significantly lower in PLTP deficient mice, indicating reduced systemic inflammation. These data suggest that PLTP appears to be playing a pro-atherogenic role in diet induced hyperlipidemic mice.
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