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

Takeshi Fujisawa, Keqing Wang, Xi-Lin Niu, Stuart Egginton, Shakil Ahmad, Peter W. Hewett, Christopher D. Kontos, Asif Ahmed*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalCardiovascular Research
Volume113
Issue number1
DOIs
Publication statusPublished - 17 Oct 2017

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Bibliographical note

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Funding: British Heart Foundation (PG/06/114); MRC (G0601295 and G0700288); NIH (R01 HL70165); and Mid-Atlantic Affiliate of the American Heart Association (0355792U)

Keywords

  • angiopoietin-1
  • atherosclerosis
  • monocytes

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