We demonstrated in a previous study that murine double minute (Mdm)-2 is essential for exerciseinduced skeletal muscle angiogenesis. In the current study, we investigated the mechanisms that regulate Mdm2 activity in response to acute exercise and identified VEGF-A as a key stimulator of Mdm2 phosphorylation on Ser 166

Angioadaptation is the ability of capillaries to adapt to physiological changes. This is influenced by interactions between endothelial cells (EC) and supporting cells such as myofibroblasts (MF).ObjectiveWe examined a possible pro‐angiogenic paracrine interaction between newly identified MF progenitors in human skeletal muscle and primary EC, and how this interaction may be altered under hyperglycemic conditions.MethodsHuman skeletal muscle MF progenitor cells (CD90+) were sorted by FACS and differentiated into MF using TGFb under normo‐(NG) or hyperglycemic (HG) conditions. The expression level of 55 angioadaptive proteins was measured by proteome array in the conditioned media (secretome). Human microvascular EC were treated with secretome. VEGF‐A and TSP‐1 mRNA levels were measured by qPCR in these cells. EC migration was evaluated in the Boyden Chamber assay.ResultsThe secretome from differentiated MF was enriched in pro‐angiogenic factors compared to CD90+ cells. VEGF‐A mRNA expression was increased in EC when treated with MF secretome and their migration was stimulated. In contrast, CD90+ cell differentiation under HG resulted in decreased pro‐angiogenic factor secretion in MF secretome and reduced EC migration.ConclusionMF exert some pro‐angiogenic stimulation on primary EC compared to progenitor cells. This pro‐angiogenic effect is attenuated when cell differentiation occurs under HG. Funding: CIHR/NSERC.