Van Eck, Miranda and Bos, I. Sophie T. and Kaminski, Wolfgang E. and Orso, Evelyn and Rothe, Gregor and Twisk, Jaap and Boettcher, Alfred and Van Amersfoort, Edwin S. and Christiansen-Weber, Trudy A. and Fung-Leung, Wai-Ping and Van Berkel, Theo J. C. and Schmitz, Gerd (2002) Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 99 (9). pp. 6298-6303. ISSN 0027-8424
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BINDING CASSETTE TRANSPORTER-1; DENSITY-LIPOPROTEIN DEFICIENCY; AMERICAN-HEART-ASSOCIATION; TANGIER-DISEASE; APOLIPOPROTEIN-E; HISTOLOGICAL CLASSIFICATION; VASCULAR-LESIONS; BONE-MARROW; MICE; CHOLESTEROL; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Oct 2021 16:09 |
| Last Modified: | 27 Oct 2021 16:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40373 |
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