Format

Send to

Choose Destination
Cardiovasc Res. 2017 Jan;113(1):81-89. doi: 10.1093/cvr/cvw223.

Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes.

Author information

1
Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, U.K.
2
Gustav Born Centre for Vascular Biology and BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK.
3
Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, U.K; asif.ahmed@aston.ac.uk k.wang@aston.ac.uk.
4
Department of Medicine, Division of Cardiology, Duke University Medical Centre, Durham, NC 27710, USA.
5
Multidisciplinary Cardiovascular Research Centre, School of Biological Sciences, University of Leeds, Leeds, UK.
6
Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

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.

KEYWORDS:

Angiopoietin-1 ; Atherosclerosis ; Monocytes

PMID:
28069704
PMCID:
PMC5220674
DOI:
10.1093/cvr/cvw223
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center