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
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.
Mots clés
Angiogenesis, Chronic kidney disease, Ischemia–reperfusion, Receptor for advanced glycation end products, Soluble fms-like tyrosine kinase 1
Référence
Angiogenesis. 2020 Sep 23;: