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Angiogenesis in the Ischemic Rat Lung
Published on: February 8, 2013
通过局部生长因子释放的血管再生是通过微血管清除自我限制的
Kha N Le1, Chao-Wei Hwang, A Rami Tzafriri
1Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Room E25-442, 77 Massachusetts Ave, Cambridge, MA 02139, USA. knle@mit.edu
Circulation
|May 28, 2009
概括
血管新生疗法在人类中面临挑战,因为新的血管增强药物清除,限制了它们的有效性. 这种自我调节机制可能解释了为什么有希望的益血管性治疗失败了.
科学领域:
- 心血管研究研究心血管研究
- 生物医学工程 生物医学工程
- 药理学 药理学是指药理学的学科.
背景情况:
- 人类的稳定血管再生仍然是血管生成科学的重大挑战,尽管临床前数据充满希望.
- 血管新生疗法被假设通过改变组织特征来自我调节,影响药物输送和疗效.
- 诱导的新血管化可以增加药物清除,限制保留和随后的治疗效果.
研究的目的:
- 研究血管新生疗法的自我调节机制.
- 量化诱导毛细血管流对药物清除和组织保留的影响.
- 了解血管新生因子持续局部输送的药理学复杂性.
主要方法:
- 在局部心上表皮分娩后量化纤维细胞生长因子 (FGF) 清除.
- 评估了冠状动脉 perfusion,超内膜通透性和FGF空间负荷之间的关系.
- 通过将其与糖八硫酸盐结合,验证了FGF运输的模型预测.
主要成果:
- 与依赖血管泄漏的模型相比,完整的冠状动脉输液显著降低了FGF的空间负荷.
- 增加的透性导致FGF透和保留的减少,与血管内输送相反.
- 持续的局部FGF输送诱导了新血管化,但导致了快速的药物清洗和减少透深度.
结论:
- 益血管性化合物的治疗疗效被增强的药物清除所抵消.
- 血管生成的这种固有的自我限制性质可能解释了以前有前途的益血管性疗法的临床失败.
- 了解这些药理动力学动态对于开发有效的血管生成治疗至关重要.
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