The role of receptor MAS in microglia-driven retinal vascular development

S. Foulquier*, V. Caolo, G. Swennen, I. Milanova, S. Reinhold, C. Recarti, N. Alenina, M. Bader, U. M. Steckelings, T. Vanmierlo, M. J. Post, E. A. Jones, R. J. van Oostenbrugge, T. Unger

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

Objective The receptor MAS, encoded by Mas1, is expressed in microglia and its activation has been linked to anti-inflammatory actions. However, microglia are involved in several different processes in the central nervous system, including the promotion of angiogenesis. We therefore hypothesized that the receptor MAS also plays a role in angiogenesis via microglia.

Approach and results To assess the role of MAS on vascular network development, flat-mounted retinas from 3-day-old wild-type (WT) and -Mas1(-/-) mice were subjected to Isolectin B4 staining. The progression of the vascular front was reduced (- 24%, p <0.0001) and vascular density decreased (- 38%, p <0.001) in -Mas1(-/-) compared to WT mice with no change in the junction density. The number of filopodia and filopodia bursts were decreased in -Mas1(-/-) mice at the vascular front (- 21%, p <0.05; - 29%, p <0.0001, respectively). This was associated with a decreased number of vascular loops and decreased microglial density at the vascular front in -Mas1(-/-) mice (-32%, p <0.001; - 26%, p <0.05, respectively). As the front of the developing vasculature is characterized by reduced oxygen levels, we determined the expression of Mas1 following hypoxia in primary microglia from 3-day-old WT mice. Hypoxia induced a 14-fold increase of Mas1 mRNA expression (p <0.01). Moreover, stimulation of primary microglia with a MAS agonist induced expression of Notch1 (+ 57%, p <0.05), Dll4 (+ 220%, p <0.001) and Jag1 (+ 137%, p <0.001), genes previously described to mediate microglia/endothelial cell interaction during angiogenesis.

Conclusions Our study demonstrates that the activation of MAS is important for microglia recruitment and vascular growth in the developing retina.

Original languageEnglish
Pages (from-to)481-489
Number of pages9
JournalAngiogenesis
Volume22
Issue number4
DOIs
Publication statusPublished - Nov 2019

Keywords

  • Angiogenesis
  • Renin angiotensin system
  • Angiotensin receptors
  • Macrophage
  • CNS
  • Developmental biology
  • Endothelium
  • Vascular biology
  • RENIN-ANGIOTENSIN SYSTEM
  • RAT-BRAIN
  • MATRIX-METALLOPROTEINASE
  • CANCER XENOGRAFTS
  • ANGIOGENESIS
  • EXPRESSION
  • GROWTH
  • HEALTH
  • ADULT
  • CELLS

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