Dual role of vascular endothelial growth factor family members and angiomotion in vascular and muscular plasticity during rodent skeletal muscle remodeling

骨骼肌具有显著的可塑性，能迅速适应功能需求的变化，这可以通过毛细血管和肌纤维特性的变化来证明。肌纤维产生血管内皮生长因子-A（VEGF-A），这是肌肉血管生成的关键起始物，即毛细血管的从头合成。VEGF-A还确保维持已建立的毛细血管。在骨骼肌重塑过程中，肌纤维主要通过调节VEGF-A的表达来调节肌肉毛细血管的形成，而VEGF-A的表达反过来又会促进血管生成或诱导血管退化。最近的证据表明，肌肉毛细血管的调制，继发于VEGF-A表达的肌纤维，可以控制肌纤维的收缩表型的变化。此外，最近的数据表明，VEGF-A也可以影响肌肉细胞的代谢特性。因此，我推测VEGF-A的表达肌纤维将影响他们的收缩和代谢表型在骨骼肌remodeling. Also，回归，维持或刺激肌肉毛细血管不能解释VEGF-A单独。在血管生成因子中，血管内皮生长因子-B和血管动蛋白在骨骼肌中高度表达。此外，它们的作用不仅限于毛细作用调节。因此，我假设，除了他们参与血管生成，这些分子可以发挥作用，在肌肉细胞remodeling.The我的研究计划的总体目标是调查是否VEGF-A，VEGF-B和angiomotin，最初描述在血管生成，发挥双重作用的毛细血管和肌纤维。因此，通过作用于内皮细胞和肌细胞，它们可能对肌肉重塑至关重要。NSERC提案中提出的计划将为了解这些分子在啮齿动物骨骼肌重塑过程中对肌肉和血管可塑性所起的基本作用带来新的知识。

Skeletal muscle rapidly adapts to variations of the functional demand with a remarkable plasticity that can be evidenced by changes in capillarity and myofibres' properties.Myofibres produce vascular endothelial growth factor-A (VEGF-A), a key initiator of muscular angiogenesis, i.e. the de novo synthesis of blood capillaries. VEGF-A also ensures the maintenance of established capillaries. During skeletal muscle remodeling, myofibres could thus adjust muscle capillarity mainly by modulating VEGF-A expression that would in turn either enhance angiogenesis or induce vascular regression.However this relationship between myofibres, VEGF-A and capillaries is likely much more complex. Recent evidences suggest that the modulation of muscle capillarity, secondary to VEGF-A expression by myofibres, could control changes in the myofibres' contractile phenotype. In addition, recent data have shown that VEGF-A could also affect the metabolic properties of muscle cells. I therefore hypothesize that VEGF-A expression by myofibres will affect both their contractile and metabolic phenotypes during skeletal muscle remodeling.Moreover, regression, maintenance or stimulation of muscle capillarity cannot be explained by VEGF-A alone. Among angiogenesis factors, the vascular endothelial growth factor-B and angiomotin are highly expressed in skeletal muscle. Furthermore, their action is not restricted to capillarity regulation only. I thus hypothesize that aside from their involvement in angiogenesis, these molecules could play a role in muscle cells remodeling.The overall aim of my research program is to investigate whether VEGF-A, VEGF-B and angiomotin, initially described during angiogenesis, play a dual role on capillaries and myofibres. Thus, by acting on both endothelial cells and myocytes, they could be of critical importance for muscle remodeling. The program presented in this NSERC proposal will bring new knowledge in understanding the fundamental roles played by these molecules on both muscular and vascular plasticity during rodent skeletal muscle remodeling.