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

Research output: Contribution to journalArticle

Colleges, School and Institutes

External organisations

  • Duke University Medical Center, Durham, North Carolina, United States of America.
  • EDINBURGH UNIVERSITY
  • Aston University
  • University of Leeds

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.

Details

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalCardiovascular Research
Volume113
Issue number1
Early online date9 Jan 2017
Publication statusE-pub ahead of print - 9 Jan 2017

Keywords

  • Angiopoietin-1, Atherosclerosis, Monocytes