Angioadaptive Allies: Examining the Relationship Between Endothelial Cells and Human Skeletal Muscle Myofibroblasts

Angioadaptation is the ability of capillaries to adapt to physiological changes. This is influenced by interactions between endothelial cells and supporting cells such as myofibroblasts. We examined a possible pro-angiogenic paracrine interaction between primary human dermal microvascular endothelial cells (HDMECs) and newly identified myofibroblast (MyoFib) progenitors in human skeletal muscle, and how this interaction may be altered under hyperglycemic conditions. Human skeletal muscle Myofib progenitor cells (CD90+) were sorted by FACS and differentiated into MyoFib using TGFβ under normo- (NG) or hyperglycemic (HG) conditions. The expression level of 55 angioadaptive proteins was measured by proteome array in the conditioned media. HDMECs were then treated with the conditioned media. VEGF-A, TSP-1 mRNA expression, and VEGF-A, TSP-1, p38, p-p38, and p-VEGF-R2 protein levels were measured by qPCR and western blot respectively. HDMEC migration was evaluated in the Boyden Chamber assay. HDMECs were also subjected to chronic HG and analyzed. MyoFib exert some pro-angiogenic stimulation on HDMECs compared to progenitor cells. This pro-angiogenic effect is attenuated when cell differentiation occurs under HG.