Multi-scale computational models of pro-angiogenic treatments in peripheral arterial disease
Multi-scale computational models of pro-angiogenic treatments in peripheral arterial disease
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DOI：
10.1007/s10439-007-9303-0
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发表时间：
2007-06-01
影响因子：
3.8
通讯作者：
Popel, Aleksander S.
中科院分区：
文献类型：
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作者：
Mac Gabhann, Feilim;Ji, James W.;Popel, Aleksander S.
诱导血管生成是改善外周动脉疾病(PAD)的一种很有前途的治疗策略。这种闭塞性疾病导致肌肉缺血，而新生血管是增加组织灌注量的途径。血管内皮细胞生长因子(VEGF)家族是一类强大的促血管生成细胞因子，是一种潜在的治疗剂，可以增加组织血管上的血管内皮生长因子受体信号。为了研究可能的治疗方法对组织内血管内皮生长因子浓度和梯度的影响，我们考虑了三种策略：血管内皮生长因子基因治疗(例如腺相关病毒)；血管内皮生长因子细胞治疗(注射过表达血管内皮生长因子的成肌细胞)；和慢性运动(上调血管内皮生长因子受体的表达)。用于研究这些策略的多尺度计算模型是几个组成部分的集成：肌肉几何形状和细胞类型的解剖学描述；微血管血流量；组织氧分布；肌肉纤维分泌的血管内皮生长因子；血管内皮生长因子在间质中的运输；以及微血管内皮细胞上的血管内皮生长因子受体结合。运动训练可增加低氧组织中血管内皮生长因子的分泌，增加血管内皮生长因子受体的表达，使血管内皮细胞生长因子浓度和血管内皮细胞生长因子梯度均增加，预计运动训练比单纯应用血管内皮细胞生长因子的治疗更有效。
The induction of angiogenesis is a promising therapeutic strategy for the amelioration of peripheral arterial disease (PAD). This occlusive disease results in muscle ischemia, and neovascularization is a route to increasing the perfusion in the tissue. The vascular endothelial growth factor (VEGF) family of potent pro-angiogenic cytokines is a potential therapeutic agent, increasing VEGF-receptor signaling on tissue vasculature. To investigate the effects of possible therapies on the VEGF concentrations and gradients within the tissue, we consider three such strategies: VEGF gene therapy (e.g. by adeno-associated virus); VEGF cell-based therapy (injected myoblasts that overexpress VEGF); and chronic exercise (which upregulates VEGF receptor expression). The multi-scale computational model used to investigate these strategies is an integration of several components: an anatomical description of the muscle geometry and cell types; microvascular blood flow; tissue oxygen distribution; VEGF secretion from muscle fibers; VEGF transport through interstitial space; and VEGF-receptor binding on microvascular endothelial cells. Exercise training, which results in increased VEGF secretion in hypoxic tissue and increased VEGF receptor expression, exhibits increases in both VEGF concentration and VEGF gradients, and is predicted to be more effective than the other, VEGF-only treatments.