1. Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes
- Author
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Takeshi, Fujisawa, Keqing, Wang, Xi-Lin, Niu, Stuart, Egginton, Shakil, Ahmad, Peter, Hewett, Christopher D, Kontos, and Asif, Ahmed
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Genetic Vectors ,Aortic Diseases ,Aorta, Thoracic ,Diet, High-Fat ,Monocytes ,Adenoviridae ,Tissue Culture Techniques ,Apolipoproteins E ,Vascular Biology ,Angiopoietin-1 ,Animals ,Antigens, Ly ,Humans ,Genetic Predisposition to Disease ,Chemokine CCL2 ,Mice, Knockout ,CD11b Antigen ,Original Articles ,Atherosclerosis ,Plaque, Atherosclerotic ,Mice, Inbred C57BL ,Disease Models, Animal ,Phenotype ,Signal Transduction - Abstract
Aims Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse. Methods and results Apo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced. Conclusions Ang-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.
- Published
- 2016