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Erschienen in: Angiogenesis 4/2012

01.12.2012 | Original Paper

RANTES/CCL5-induced pro-angiogenic effects depend on CCR1, CCR5 and glycosaminoglycans

verfasst von: N. Suffee, H. Hlawaty, A. Meddahi-Pelle, L. Maillard, L. Louedec, O. Haddad, L. Martin, C. Laguillier, B. Richard, O. Oudar, D. Letourneur, N. Charnaux, A. Sutton

Erschienen in: Angiogenesis | Ausgabe 4/2012

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Abstract

Atherosclerosis involves angiogenesis and inflammation with the ability of endothelial cells and monocytes to respond to chemokines. We addressed here by in vitro and in vivo approaches, the role of the chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES)/CCL5 on angiogenesis through its receptors CCR1, CCR5, syndecan-1 (SDC-1), syndecan-4 (SDC-4) and CD-44. Our data demonstrate that RANTES/CCL5 is pro-angiogenic in a rat subcutaneous model. This RANTES/CCL5-activity may be related to the in vitro promotion of endothelial cell migration, spreading and neo-vessel formation. RANTES/CCL5-mediated angiogenesis depends at least partly on Vascular Endothelial Growth Factor (VEGF) secretion by endothelial cells, since this effect is decreased when endothelial cells are incubated with anti-VEGF receptor antibodies. RANTES/CCL5-induced chemotaxis is mediated by matrix metalloproteinase-9. We demonstrate that specific receptors of RANTES/CCL5 such as G protein-coupled receptors CCR1 and CCR5, and heparan sulfate proteoglycans, SDC-1, SDC-4 or CD-44, play a major role in RANTES/CCL5-induced angiogenic effects. By the use of two RANTES/CCL5 mutants, [E66A]-RANTES/CCL5 with impaired ability to oligomerize, and [44AANA47]-RANTES/CCL5 mutated in the main RANTES/CCL5-glycosaminoglycan (GAG) binding site, we demonstrate that chemokine oligomerization and binding to GAGs are essential in RANTES/CCL5-induced angiogenic effects. According to these results, new therapeutic strategies based on RANTES/CCL5 can be proposed for neo-angiogenesis after vascular injury. Mutants of RANTES/CCL5 may also represent an innovative approach to prevent the angiogenesis associated with the formation of atherosclerotic plaque.
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Metadaten
Titel
RANTES/CCL5-induced pro-angiogenic effects depend on CCR1, CCR5 and glycosaminoglycans
verfasst von
N. Suffee
H. Hlawaty
A. Meddahi-Pelle
L. Maillard
L. Louedec
O. Haddad
L. Martin
C. Laguillier
B. Richard
O. Oudar
D. Letourneur
N. Charnaux
A. Sutton
Publikationsdatum
01.12.2012
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 4/2012
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-012-9285-x

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