Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
Curr Mol Med. 2009 Nov;9(8):967-72. doi: 10.2174/156652409789712747.
The idea of delivery of proangiogenic factors to the ischemic region of myocardium or skeletal muscles was proposed more than 30 years ago and abundant preclinical data validate this concept. However, clinical experience with this approach has generally produced unfulfilled promises. Although reestablishment of functional collateral networks for improvement of blood perfusion in ischemic tissues is an undisputed concept for therapeutic intervention, the molecular mechanism underlying collaterogenesis under tissue hypoxia remains poorly understood. Critical issues including the therapeutic efficacy of monotherapy vs. combination with arteriogenic therapy, drug release, optimal dose, and time scale of delivery remain to be resolved. The aim of this review is to discuss molecular mechanisms of angiogenesis and arteriogenesis, to better design clinical trials, and to improve therapeutic efficacy of proangiogenic and arteriogenic factors for the treatment of ischemic diseases.
将促血管生成因子递送至心肌或骨骼肌缺血区域的想法早在 30 多年前就已提出，丰富的临床前数据验证了这一概念。然而，这种方法的临床经验通常未能兑现承诺。尽管重建功能性侧支网络以改善缺血组织的血液灌注是治疗干预的公认概念，但组织缺氧下侧支生成的分子机制仍知之甚少。包括单药治疗与联合动脉生成治疗的疗效、药物释放、最佳剂量和递药时间尺度等关键问题仍有待解决。本文的目的是讨论血管生成和动脉生成的分子机制，以更好地设计临床试验，并提高促血管生成和动脉生成因子治疗缺血性疾病的治疗效果。
