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

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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.

OriginalsprogEngelsk
TidsskriftAngiogenesis
Vol/bind22
Sider (fra-til)481-489
ISSN0969-6970
DOI
StatusUdgivet - 20. jun. 2019

Fingeraftryk

Microglia
Pseudopodia
Retina
Chemical activation
Endothelial cells
Neurology
Lectins
Cell Communication
Anti-Inflammatory Agents
Central Nervous System
Genes
Oxygen
Messenger RNA
Growth

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Foulquier, S., Caolo, V., Swennen, G., Milanova, I., Reinhold, S., Recarti, C., ... Unger, T. (2019). The role of receptor MAS in microglia-driven retinal vascular development. Angiogenesis, 22, 481-489. https://doi.org/10.1007/s10456-019-09671-3
Foulquier, S ; Caolo, V ; Swennen, G ; Milanova, I ; Reinhold, S ; Recarti, C ; Alenina, N ; Bader, M ; Steckelings, U M ; Vanmierlo, T ; Post, M J ; Jones, E A ; van Oostenbrugge, R J ; Unger, T. / The role of receptor MAS in microglia-driven retinal vascular development. I: Angiogenesis. 2019 ; Bind 22. s. 481-489.
@article{2fc3c281648144d8b398982731687d34,
title = "The role of receptor MAS in microglia-driven retinal vascular development",
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.",
keywords = "Angiogenesis, Angiotensin receptors, CNS, Developmental biology, Endothelium, Macrophage, Renin angiotensin system, Vascular biology",
author = "S Foulquier and V Caolo and G Swennen and I Milanova and S Reinhold and C Recarti and N Alenina and M Bader and Steckelings, {U M} and T Vanmierlo and Post, {M J} and Jones, {E A} and {van Oostenbrugge}, {R J} and T Unger",
year = "2019",
month = "6",
day = "20",
doi = "10.1007/s10456-019-09671-3",
language = "English",
volume = "22",
pages = "481--489",
journal = "Angiogenesis",
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Foulquier, S, Caolo, V, Swennen, G, Milanova, I, Reinhold, S, Recarti, C, Alenina, N, Bader, M, Steckelings, UM, Vanmierlo, T, Post, MJ, Jones, EA, van Oostenbrugge, RJ & Unger, T 2019, 'The role of receptor MAS in microglia-driven retinal vascular development', Angiogenesis, bind 22, s. 481-489. https://doi.org/10.1007/s10456-019-09671-3

The role of receptor MAS in microglia-driven retinal vascular development. / Foulquier, S; Caolo, V; Swennen, G; Milanova, I; Reinhold, S; Recarti, C; Alenina, N; Bader, M; Steckelings, U M; Vanmierlo, T; Post, M J; Jones, E A; van Oostenbrugge, R J; Unger, T.

I: Angiogenesis, Bind 22, 20.06.2019, s. 481-489.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The role of receptor MAS in microglia-driven retinal vascular development

AU - Foulquier, S

AU - Caolo, V

AU - Swennen, G

AU - Milanova, I

AU - Reinhold, S

AU - Recarti, C

AU - Alenina, N

AU - Bader, M

AU - Steckelings, U M

AU - Vanmierlo, T

AU - Post, M J

AU - Jones, E A

AU - van Oostenbrugge, R J

AU - Unger, T

PY - 2019/6/20

Y1 - 2019/6/20

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Angiotensin receptors

KW - CNS

KW - Developmental biology

KW - Endothelium

KW - Macrophage

KW - Renin angiotensin system

KW - Vascular biology

U2 - 10.1007/s10456-019-09671-3

DO - 10.1007/s10456-019-09671-3

M3 - Journal article

C2 - 31240418

VL - 22

SP - 481

EP - 489

JO - Angiogenesis

JF - Angiogenesis

SN - 0969-6970

ER -

Foulquier S, Caolo V, Swennen G, Milanova I, Reinhold S, Recarti C et al. The role of receptor MAS in microglia-driven retinal vascular development. Angiogenesis. 2019 jun 20;22:481-489. https://doi.org/10.1007/s10456-019-09671-3