Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes
| Autor: | Takeshi, Fujisawa, Keqing, Wang, Xi-Lin, Niu, Stuart, Egginton, Shakil, Ahmad, Peter, Hewett, Christopher D, Kontos, Asif, Ahmed |
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| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Cardiovascular Research |
| ISSN: | 1755-3245 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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