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

血管内皮生长因子家族成员和血管运动在啮齿动物骨骼肌重塑过程中血管和肌肉可塑性中的双重作用

• 批准号: 341258-2007
• 负责人: Birot, Olivier
• 金额: $ 2.09万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=364261
• 关键词: Dual; role; vascular; endothelial; growth

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.

骨骼肌迅速适应功能需求的变化，具有显著的可塑性，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发起者，即毛细血管的重新合成。VEGF-A还能确保已建立毛细血管的维持。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，进而促进血管生成或诱导血管退化。然而，肌纤维、VEGF-A和毛细血管之间的关系可能要复杂得多。最近的证据表明，肌肉毛细血管的调节，继发于肌纤维VEGF-A的表达，可以控制肌纤维收缩表型的变化。此外，最近的数据显示VEGF-A也可以影响肌肉细胞的代谢特性。因此，我假设在骨骼肌重塑过程中，肌纤维中VEGF-A的表达会影响其收缩和代谢表型。此外，肌肉毛细血管的消退、维持或刺激不能仅由VEGF-A来解释。血管生成因子中，血管内皮生长因子- b和血管运动素在骨骼肌中高度表达。此外，它们的作用不仅限于毛细血管调节。因此，我假设除了参与血管生成外，这些分子还可能在肌肉细胞重塑中发挥作用。我的研究计划的总体目标是调查VEGF-A， VEGF-B和血管运动素是否在血管生成过程中最初描述，在毛细血管和肌纤维中发挥双重作用。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。在NSERC提案中提出的计划将为理解这些分子在啮齿动物骨骼肌重塑过程中肌肉和血管可塑性所起的基本作用带来新的知识。