Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes.
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.
Duke Scholars
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Related Subject Headings
- Vascular Endothelial Growth Factor A
- Tissue Culture Techniques
- Signal Transduction
- Plaque, Atherosclerotic
- Phenotype
- Monocytes
- Mice, Knockout
- Mice, Inbred C57BL
- Male
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vascular Endothelial Growth Factor A
- Tissue Culture Techniques
- Signal Transduction
- Plaque, Atherosclerotic
- Phenotype
- Monocytes
- Mice, Knockout
- Mice, Inbred C57BL
- Male
- Humans