Hyperglycaemia-induced methylglyoxal accumulation potentiates VEGF resistance of diabetic monocytes through the aberrant activation of tyrosine phosphatase SHP-2/SRC kinase signalling axis.

ABSTRACT: Diabetes mellitus (DM) is a major cardiovascular risk factor contributing to cardiovascular complications by inducing vascular cell dysfunction. Monocyte dysfunction could contribute to impaired arteriogenesis response in DM patients. DM monocytes show blunted chemotactic responses to arteriogenic stimuli, a condition termed as vascular endothelial growth factor (VEGF) resistance. We hypothesize that methylglyoxal (MG), a glucose metabolite, induces monocyte dysfunction and aimed to elucidate the underlying molecular mechanisms. Human monocytes exposed to MG or monocytes from DM patients or mice (db/db) showed VEGF-resistance secondary to a pro-migratory phenotype. Mechanistically, DM conditions or MG exposure resulted in the upregulation of the expression of SHP-2 phosphatase. This led to

SUBMITTER: Dorenkamp M 

PROVIDER: S-EPMC6168515 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature