Slopack D, Roudier E, Liu ST, Nwadozi E, Birot O, Haas TL. Forkhead BoxO transcription factors restrain exercise-induced angiogenesis. J Physiol. 2014 Sep 15;592(Pt 18):4069-82.
Aerobic exercise training induces numerous adaptations within muscle that facilitate enhanced performance. One such adaptation is a growth of new capillaries, which bring more oxygen and nutrients to the muscle. Exercising muscles produce more of the growth factor that stimulates capillary growth. Paradoxically, new capillary growth does not occur until after multiple training sessions even though the necessary growth factors are increased after the very first session. In this, study, we identified a protein made by capillaries that acts to prevent new capillary growth. We found that this protein, Forkhead BoxO (FoxO), is produced after a single exercise bout, and that this level gradually decreases with repeated exercise. Using transgenic mice with an inducible deletion of FoxO, we found that exercise induced capillary growth was accelerated substantially in mice lacking FoxO. Our study demonstrates that FoxO proteins play an important role in establishing how rapidly exercising muscle can undergo the growth of new capillaries. These findings have application to understanding how to optimize performance through stimulating the appropriate muscle adaptations to exercise training. This study also helps us to understand that some individuals who have excessively high levels of FoxO proteins, as is known to occur in people with peripheral artery disease or type II diabetes, may respond poorly to exercise training.
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