Abstract |
The mechanisms that promote an inflammatory environment and accelerated atherosclerosis in diabetes are poorly understood. We show that macrophages isolated from two different mouse models of type 1 diabetes exhibit an inflammatory phenotype. This inflammatory phenotype associates with increased expression of long-chain acyl-CoA synthetase 1 (ACSL1), an enzyme that catalyzes the thioesterification of fatty acids. Monocytes from humans and mice with type 1 diabetes also exhibit increased ACSL1. Furthermore, myeloid-selective deletion of ACSL1 protects monocytes and macrophages from the inflammatory effects of diabetes. Strikingly, myeloid-selective deletion of ACSL1 also prevents accelerated atherosclerosis in diabetic mice without affecting lesions in nondiabetic mice. Our observations indicate that ACSL1 plays a critical role by promoting the inflammatory phenotype of macrophages associated with type 1 diabetes; they also raise the possibilities that diabetic atherosclerosis has an etiology that is, at least in part, distinct from the etiology of nondiabetic vascular disease and that this difference is because of increased monocyte and macrophage ACSL1 expression.
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Authors | Jenny E Kanter, Farah Kramer, Shelley Barnhart, Michelle M Averill, Anuradha Vivekanandan-Giri, Thad Vickery, Lei O Li, Lev Becker, Wei Yuan, Alan Chait, Kathleen R Braun, Susan Potter-Perigo, Srinath Sanda, Thomas N Wight, Subramaniam Pennathur, Charles N Serhan, Jay W Heinecke, Rosalind A Coleman, Karin E Bornfeldt |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 109
Issue 12
Pg. E715-24
(Mar 20 2012)
ISSN: 1091-6490 [Electronic] United States |
PMID | 22308341
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Glucose
- Lipids
- Receptors, LDL
- Coenzyme A Ligases
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Topics |
- Alleles
- Animals
- Atherosclerosis
(metabolism)
- Blood Glucose
(metabolism)
- Bone Marrow Transplantation
- Coenzyme A Ligases
(metabolism)
- Diabetes Mellitus
(metabolism)
- Female
- Gene Deletion
- Humans
- Inflammation
- Lipids
(chemistry)
- Macrophages
(cytology)
- Male
- Mice
- Mice, Transgenic
- Models, Biological
- Monocytes
(cytology)
- Phenotype
- Receptors, LDL
(genetics)
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