Angiopoietin-1 induces migration of monocytes in a tie-2 and integrin-independent manner

Shakil Ahmad, Melissa J. Cudmore, Keqing Wang, Peter W. Hewett, Rahul Potluri, Takeshi Fujisawa, Asif Ahmed

Research output: Contribution to journalArticle

Abstract

Angiopoietin-1 (Ang-1) is an angiogenic growth factor that activates Tie-2 and integrins to promote vessel wall remodeling. The recent finding of the potential proatherogenic effects of Ang-1 prompted us to investigate whether Ang-1 promotes monocyte chemotaxis, endothelial binding, and transendothelial migration, key events in the progression of atherosclerosis. Here, we show that Ang-1 induces chemotaxis of monocytes in a manner that is independent of Tie-2 and integrin binding but dependent on phosphoinositide 3-kinase and heparin. In addition, Ang-1 promoted phosphoinositide 3-kinase-dependent binding of monocytes to endothelial monolayers and stimulated transendothelial migration. Fluorescence-activated cell sorting analysis showed that exogenous Ang-1 adheres directly to monocytes as well as to human umbilical endothelial cells, but neither Tie-2 mRNA nor protein were expressed by primary monocytes. Although Ang-1 binding to human umbilical endothelial cells was partially Tie-2 and integrin dependent, Ang-1 binding to monocytes was independent of these factors. Finally, preincubation of monocytes with soluble heparin abrogated Ang-1 binding to monocytes and migration, and partially prevented Ang-1 binding to human umbilical endothelial cells. In summary, Ang-1 induces chemotaxis of monocytes by a mechanism that is dependent on phosphoinositide 3-kinase and heparin but independent of Tie-2 and integrins. The ability of Ang-1 to recruit monocytes suggests it may play a role in inflammatory angiogenesis and may promote atherosclerosis.
Original languageEnglish
Pages (from-to)477-483
Number of pages7
JournalHypertension
Volume56
Issue number3
DOIs
Publication statusPublished - Sep 2010

Keywords

  • angiopoietin-1
  • Tie-2
  • monocytes
  • chemotaxis
  • vascular
  • phosphoinositide 3-kinase
  • endothelium

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