Angio-adaptation in unloaded skeletal muscle: new insights into an early and muscle type-specific dynamic process

With a remarkable plasticity, skeletal muscle adapts to an altered functional demand. Muscle angio-adaptation can either involve the growth or the regression of capillaries as respectively observed in response to endurance training or muscle unloading. Whereas the molecular mechanisms that regulate exercise-induced muscle angiogenesis have been extensively studied, understanding how muscle unloading can in contrast lead to capillary regression has received very little attention. Here we have investigated the consequences of a 9 day time course hindlimb unloading on both capillarization and expression of angio-adaptive molecules in two different rat skeletal muscles. Both soleus and plantaris muscles were atrophied similarly. In contrast, our results have shown different angio-adaptive patterns between these two muscles. Capillary regression occurred only in the soleus, a slow-twitch and oxidative postural muscle. Conversely, the level of capillarization was preserved in the plantaris, a fast-twitch and glycolytic muscle. We have also measured the time course protein expression of key pro- and anti-angiogenic signals (VEGF-A, VEGF-B, VEGF-R2, TSP-1). Our results have revealed that the angio-adaptive response to unloading was muscle-type specific, and that an integrated balance between pro- and anti-angiogenic signals plays a determinant role in regulating this process. In conclusion, we have brought new evidence that measuring the ratio between pro- and anti-angiogenic signals in order to evaluate muscle angio-adaptation was a more accurate approach than analysing the expression of molecular factors taken individually.