文章基本信息

标题：Macrophage PLTP is atheroprotective in LDLr-deficient mice with systemic PLTP deficiency
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作者：David T. Valenta ; Joshua J. Bulgrien ; David J. Bonnet 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：1
页码：24-32
DOI：10.1194/jlr.M700228-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Systemic phospholipid transfer protein (PLTP) is a recognized risk factor for coronary heart disease. In apolipoprotein E-deficient mice, systemic PLTP deficiency is atheroprotective, whereas PLTP overexpression is proatherogenic. As expected, we also observed significantly smaller lesions ( P −/−) PLTP-deficient (PLTP^−/−) mice compared with LDLr^−/− mice expressing systemic PLTP. To assess the specific contribution of only macrophage-derived PLTP to atherosclerosis progression, bone marrow transplantation was performed in LDLr^−/− mice that also lacked systemic PLTP. Groups of double mutant PLTP^−/−LDLr^−/− mice were irradiated with 1,000 rad and injected with bone marrow (BM) cells collected from either PLTP^−/− or wild-type mice. When fed a high-fat diet, BM cell expression of PLTP decreased plasma cholesterol of PLTP^−/−LDLr^−/− mice from 878 ± 220 to 617 ± 183 mg/dl and increased HDL cholesterol levels from 54 ± 11 to 117 ± 19 mg/dl. This decreased total plasma cholesterol and increased HDL cholesterol contributed to the significantly smaller atherosclerotic lesions in both aortas and heart sinus valves observed in these mice. Thus, unlike total systemic PLTP, locally produced macrophage-derived PLTP beneficially alters lipoprotein metabolism and reduces lesion progression in hyperlipidemic mice.