NDLI: Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues.

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Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues.

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Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kaminski, Wolfgang E. Orsó, Evelyn Van Eck, Miranda Van Amersfoort, Edwin S. Twisk, Jaap Van Berkel, Theo J. C. Rothe, Gregor Fung-leung, Wai-ping Böttcher, Alfred Christiansen-weber, Trudy A. Schmitz, Gerd Bos, I. Sophie T.
Description	Author Affiliation: van Eck M ( Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden University, P.O. Box 9503, 2300 RA Leiden, The Netherlands. M.Eck@LACDR.LeidenUniv.nl);
Abstract	The ATP-binding cassette transporter 1 (ABCA1) has recently been identified as a key regulator of high-density lipoprotein (HDL) metabolism, which is defective in familial HDL-deficiency syndromes such as Tangier disease. ABCA1 functions as a facilitator of cellular cholesterol and phospholipid efflux, and its expression is induced during cholesterol uptake in macrophages. To assess the role of macrophage ABCA1 in atherosclerosis, we generated low-density lipoprotein (LDL) receptor knockout (LDLr(-/-)) mice that are selectively deficient in leukocyte ABCA1 (ABCA1(-/-)) by using bone marrow transfer (ABCA1(-/-) --> LDLr(-/-)). Here we demonstrate that ABCA1(-/-) --> LDLr(-/-) chimeras develop significantly larger and more advanced atherosclerotic lesions compared with chimeric LDLr(-/-) mice with functional ABCA1 in hematopoietic cells. Targeted disruption of leukocyte ABCA1 function did not affect plasma HDL cholesterol levels. The amount of macrophages in liver and spleen and peripheral blood leukocyte counts is increased in the ABCA1(-/-) --> LDLr(-/-) chimeras. Our results provide evidence that leukocyte ABCA1 plays a critical role in the protection against atherosclerosis, and we identify ABCA1 as a leukocyte factor that controls the recruitment of inflammatory cells.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	ATP-Binding Cassette Transporters Physiology Arteriosclerosis Genetics Genetic Predisposition To Disease Leukocytes Metabolism Macrophages ATP Binding Cassette Transporter 1 Animals Aorta Apolipoproteins Bone Marrow Cells Cholesterol Lipids Blood Liver Mice Mice, Knockout Models, Genetic Spleen Time Factors Triglycerides Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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