Unravelling the mysteries of exercise-induced angiogenesis
We all know that exercise is good for the body and your health. But did you know that whenever you run, spin or shoot hoops, you’re also creating new blood vessels? “Muscles in motion require more blood, and to get it, they grow more vessels, a process called angiogenesis,” says Katrien De Bock, a professor of Exercise and Health at ETH Zurich. “In fact, exercise is one of the very few physiological circumstances under which functional blood vessels are formed.” For being such an important bodily function, we know surprisingly little about the underlying molecular and cellular mechanisms of angiogenesis. “Understanding this would allow us to work towards systematically improving the blood supply of patients’ muscles,” explains De Bock.
Metabolically better prepared for angiogenesis
Considering the implications such knowledge could have for patients suffering from diabetes or arterial occlusions and in organ transplant recipients, De Bock set out to unravel the mysteries of angiogenesis. With the support of the EU-funded MusEC project, her team looked at how muscle endothelial cells reprogramme their metabolism during exercise-induced angiogenesis. “What we found was a remarkable amount of metabolic diversity within muscle endothelial cells,” notes De Bock. Specifically, the team discovered an endothelial subpopulation that is distinguished by having a regulatory protein call ATF4. According to De Bock, this subpopulation is metabolically better prepared for angiogenesis. “You could characterise these endothelial cells as being on standby mode, always ready to jump into action and start forming new vessels as soon as you jump into action and begin exercising,” she says. Researchers also investigated whether muscle endothelial cells could exploit their metabolism as a means of communicating, or crosstalking, with their microenvironment. “While we initially hypothesised that endothelial cells also communicate with muscle fibres, what we found is that they actually leverage their highly glycolytic make-up to steer muscle regeneration,” explains De Bock. “They do this by determining the functional polarisation of macrophages, the main immune effectors located inside a muscle.”
Towards developing regenerative therapies
Although the European Research Council supported MusEC project advanced our understanding of how blood vessels are formed in muscle during angiogenesis, many questions remain. “I firmly believe that further increasing our understanding about exercise-induced angiogenesis is the key to developing regenerative therapies for those conditions where impaired angiogenesis plays a crucial role,” remarks De Bock. Having established itself as a centre of expertise in the study of cellular crosstalk and muscle metabolism, De Bock’s lab plans to expand on the work done during the project. “Our discovery that endothelial cells closely crosstalk with macrophages has opened a completely new research avenue that we would like to further explore in the near future,” she concludes.
Keywords
MusEC, muscles, angiogenesis, blood vessels, regenerative therapies, diabetes, arterial occlusions, organ transplant, muscle endothelial cells, metabolism, muscle regeneration