Depression of progenitor cell function by advanced glycation endproducts (AGEs): potential relevance for impaired angiogenesis in advanced age and XXXX .

@entity2280 @entity6 @entity1435
@entity6 and ageing induce reduction and dysfunction of vascular progenitor cells. Advanced glycation endproducts (AGEs) accumulate in @entity6 and ageing. We investigated the influence of AGEs on function of @entity2280 progenitor cells. @entity2280 cells were co-cultured with HUVECs in a three-dimensional spheroid assay. Sprout length growth and incorporation of @entity2280 cells into the sprouts were analyzed under 2, 20 or 200 microg/ml AGEs. AGE-receptor expression, MAP-kinase signal transduction and apoptosis were analyzed using PCR, Western blotting and flow cytometry. In the spheroid assay, AGEs concentration-dependently cause a reduction of sprout length growth by 6+/-6 to 32+/-6% and an attenuation of progenitor cells incorporation into the sprouting endothelium by up to 43+/-6%. This functional impairment is accompanied by activation of @entity2280 cell proliferation at lower concentrations (2 or 20 microg/ml) and by apoptosis activation under 200 microg/ml AGEs. The mRNA expression of the receptors for AGEs and the AGEs-induced activation of @entity1435 and p44/42 MAP-kinases are demonstrable in @entity2280 cells. This AGEs-mediated impairment of progenitor cell function identifies a new pathophysiological mechanism of disturbed vascular adaptation in @entity6 or ageing and suggests that lowering AGEs in recipients of progenitor cell therapy might be beneficial for the success of this therapy.
