Alagebrium targets the miR-27b/TSP-1 signaling pathway to rescue N^ε-carboxymethyl-lysine-induced endothelial dysfunction.

ABSTRACT: N^ε-carboxymethyl-lysine (CML), a major isoform of advanced glycation end products (AGEs), plays a crucial role in the functional damage of diabetes mellitus. However, it is not clear whether ALT-711 (alagebrium), an inhibitor of AGEs, is capable to rescue CML-induced poor angiogenesis, as well as the underlying mechanism. MicroRNA-27b (miR-27b) promotes angiogenesis through down-regulation of anti-angiogenic protein thrombospondin-1 (TSP-1). Here, we used diabetic mice with hindlimb ischemia to investigate whether miR-27b/TSP-1 signaling is involved in the pathology of critical limb ischemia (CLI) in diabetes mellitus. We additionally examined the effect of ALT-711 on the tube formation of endothelial cells treated with CML-BSA. Compared with control group, the lower blood flow

SUBMITTER: Chen Y 

PROVIDER: S-EPMC6456531 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature