Yeh Jennifer L, Giordano Frank J
Department of Medicine, Cardiovascular Gene Therapy Program, Yale University School of Medicine, New Haven, CT, USA.
Semin Thorac Cardiovasc Surg. 2003 Jul;15(3):236-49. doi: 10.1016/s1043-0679(03)70003-3.
Stimulating new blood vessel growth in ischemic hearts or limbs is a hopeful new approach for patients with advanced vascular disease. This approach is based generally upon the hypothesis that sufficient exposure of a vascular bed to an angiogenic protein will stimulate neovascularization. Most angiogenic proteins have a markedly short serum half-life. To overcome this, researchers have turned to gene therapy to ensure continuous expression of angiogenic proteins and prolonged exposure in the targeted vascular beds. This field is still evolving, and although early clinical trial results suggest angiogenic gene therapy can be successful, many questions remain. As we continue to learn more about the complex interplay and coordinated action of the various factors involved in regulating angiogenesis, it is likely that strategies for therapeutic angiogenesis will continue to change. This review addresses the current state of angiogenic gene therapy, contrasts gene therapy with angiogenic protein delivery, describes early and recent clinical trial data, and discusses potential new directions in the field.
刺激缺血心脏或肢体中的新血管生长，对于患有晚期血管疾病的患者来说是一种充满希望的新方法。这种方法通常基于这样一种假设，即血管床充分暴露于血管生成蛋白会刺激新血管形成。大多数血管生成蛋白的血清半衰期明显较短。为了克服这一问题，研究人员转向基因治疗，以确保血管生成蛋白的持续表达，并在目标血管床中延长暴露时间。该领域仍在不断发展，尽管早期临床试验结果表明血管生成基因治疗可能会取得成功，但仍有许多问题存在。随着我们继续深入了解调节血管生成的各种因素之间复杂的相互作用和协同作用，治疗性血管生成的策略可能会继续发生变化。本综述阐述了血管生成基因治疗的现状，将基因治疗与血管生成蛋白递送进行了对比，描述了早期和近期的临床试验数据，并讨论了该领域潜在的新方向。
