Muscle angiogenesis

During exercise, the uptake of oxygen and nutrients increases dramatically to meet the metabolic demand of the contracting muscle. For instance, total body glucose turnover can increase to more than 12 times of its resting values, and this is largely accounted for by enhanced muscle glucose utilization. To meet this metabolic demand, blood flow through the vessels surrounding the active muscle fibers is enhanced within seconds and soon the formation of new vessels from pre-existing ones, a highly dynamic and tightly controlled process termed angiogenesis, is promoted.

Angiogenesis is initiated by the secretion of growth factors – the vascular endothelial growth factor VEGF is the best described one - from a hypoxic environment. To grow under low oxygen conditions, ECs rely on a special metabolic machinery (for review see De Bock et al., Cell Metabolism 2013). Indeed, even though they are located next to the blood stream - and therefore have access to the highest oxygen levels - ECs are highly glycolytic (De Bock et al., Cell 2013). However, when they need to sprout into avascular areas and form new vessels, they upregulate glycolysis even further to fuel migration and proliferation. Suppression of glycolysis via inhibition of the glycolytic regulator PFKFB3 (phosphofructokinase-2/fructose-2,6-bisphosphatase isoform 3) in endothelial cells prevents blood vessel growth in the retina of the mouse pup and also in various models of pathological angiogenesis (De Bock et al., Cell 2013 and Schoors et al. Cell Metabolism 2013). While we now know that ECs are metabolically preconditioned to rapidly form new vessels, it remains an outstanding question whether this also holds true in muscle.

In the Laboratory of Exercise and Health, we aim to investigate whether muscle endothelial cells need to reprogram their metabolism to promote optimal muscle angiogenesis.