AgeR deletion decreases soluble fms-like tyrosine kinase 1 production and improves post-ischemic angiogenesis in uremic mice.

Fiche publication

Date publication

septembre 2020

Journal

Angiogenesis

Auteurs

Membres identifiés du Cancéropôle Est :
Pr NGUYEN Philippe , Dr TERRYN Christine , Dr BOULAGNON-ROMBI Camille

Tous les auteurs :
Dupont V, Al-Rifai R, Poitevin G, Ortillon J, Jayyosi L, Terryn C, Francois C, Rieu P, Fritz G, Boulagnon-Rombi C, Fichel C, Schmidt AM, Tournois C, Nguyen P, Touré F

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32989644

Résumé

Peripheral arterial disease occurs more frequently and has a worse prognosis in patients with chronic kidney disease (CKD). The receptor for advanced glycation end products (RAGE) is involved in multiple aspects of uremia-associated vasculopathy. Previous data suggest that the RAGE pathway may promote soluble fms-like tyrosine kinase 1 (sFlt1) production, an anti-angiogenic molecule. Thus, we tested the hypothesis that the deletion of AgeR would decrease sFlt1 production and improve post-ischemic revascularization in uremic condition. We used a well-established CKD model (5/6 nephrectomy) in WT and AgeR C57/Bl6 mice. Hindlimb ischemia was induced by femoral artery ligation. Revascularization was evaluated by complementary approaches: ischemic limb retraction, LASCA imagery, and capillary density. The production of sFlt1 was assessed at both RNA and protein levels. After hindlimb ischemia, uremic mice showed slower functional recovery (p < 0.01), decreased reperfusion (p < 0.01), lower capillary density (p = 0.02), and increased circulating sFlt1 levels (p = 0.03). AgeR deletion restored post-ischemic angiogenesis and was protective from sFlt1 increase in uremic mice. These findings show the main role of RAGE in post-ischemic angiogenesis impairment associated with CKD. RAGE may represent a key target for building new therapeutic approaches to improve the outcome of CKD patients with PAD.