The AGE-Breaker ALT-711 Restores High Blood Flow–Dependent Remodeling in Mesenteric Resistance Arteries in a Rat Model of Type 2 Diabetes

• DOI: 10.2337/db11-0750
• Publication Date: 2012-03-15T00:18:11Z
• Authors: Mohamed L. Freidja; Kahena Tarhouni; Bertrand Toutain; Céline Fassot; Laurent Loufrani; Daniel Henrion
• Keywords: Mesenteric arteries

Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this impaired diabetes. We hypothesized that breaking advanced glycation end product (AGE) cross-links could improve mesenteric Zucker diabetic fatty (ZDF) rats compared with lean (LZ) rats. Arteries, exposed to high (HF) or normal (NF) blood flow after alternate arterial ligation vivo, were collected 2 weeks. In LZ rats, HF artery diameter was larger than NF vessels, not the case ZDF Endothelium-mediated dilation which lower further decreased arteries. Treatment AGE-breaker 4,5-dimethyl-3-phenacylthiazolium chloride (ALT-711) (3 mg/kg/day; 3 weeks) reversed diabetes-induced impairment HF-dependent remodeling. ALT-711 also improved endothelium nitric oxide-dependent relaxation Reactive oxygen species reduction restored ALT-711-treated AGEs reduced Metalloproteinase activity, necessary remodeling, and by ALT-711. Thus, targeting AGE may provide a therapeutic potential overcoming microvascular complications disorders occurring