Isner J M, Takayuki A
Department of Medicine (Cardiology), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Front Biosci. 1998 May 5;3:e49-69. doi: 10.2741/a367.
Therapeutic angiogenesis constitutes a fundamental survival mechanism that acts to preserve the integrity of tissues subjected to ischemia. Supplemental administration of angiogenic cytokines--as recombinant protein or plasmid DNA--have been shown to augment collateral development when endogenous angiogenesis is suboptimal for organ function, and thus constitute a novel therapeutic option for the treatment of cardiovascular disease. These angiogenic cytokines, all of which share in common the ability to act as mitogens for endothelial cells, do not promote angiogenesis in an indiscriminate fashion; thus angiogenic cytokines selectively produce neovascularization in the ischemic tissues. The purpose of this review is to consider the mechanisms responsible for therapeutic angiogenesis which develops endogenously as well as strategies which have been devised to augment this response. The development of blood vessels is considered from the context of the embryonic paradigm; certain principles which have emerged from studies of pathologic neovascularization; and, principally, the development of collateral blood vessels supplying ischemic tissues, either endogenously or in response to administered growth factors.
治疗性血管生成是一种基本的生存机制，其作用是维持遭受缺血的组织的完整性。当内源性血管生成不足以维持器官功能时，补充血管生成细胞因子（如重组蛋白或质粒DNA）已被证明可促进侧支血管的发育，因此构成了治疗心血管疾病的一种新的治疗选择。这些血管生成细胞因子都具有作为内皮细胞有丝分裂原的能力，但它们并非以无差别方式促进血管生成；因此，血管生成细胞因子可在缺血组织中选择性地产生新血管形成。本综述的目的是探讨内源性治疗性血管生成的机制以及为增强这种反应而设计的策略。血管生成是从胚胎模式的角度来考虑的；从病理性新血管形成的研究中得出的某些原理；以及主要是内源性或响应于施用的生长因子而供应缺血组织的侧支血管的发育。
