Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis |
| |
Authors: | Baumgartl Julia Baudler Stephanie Scherner Maximilian Babaev Vladimir Makowski Liza Suttles Jill McDuffie Marcia Tobe Kazuyuki Kadowaki Takashi Fazio Sergio Kahn C Ronald Hotamisligil Gökhan S Krone Wilhelm Linton Macrae Brüning Jens C |
| |
Institution: | Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne, D-50931 Cologne, Germany. |
| |
Abstract: | Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1beta expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2(-/-) ApoE(-/-) cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|