Institut fuer Vegetative Physiologie, Campus Charité Mitte, Charité Universitaetsmedizin Berlin Berlin, Germany.
Front Mol Neurosci. 2011 Aug 24;4:14. doi: 10.3389/fnmol.2011.00014. eCollection 2011.
Vascular growth forms the first functional organ system during development, and continues into adult life, wherein it is often associated with disease states. Genetically determined vasculogenesis produces a primary vascular plexus during ontogenesis. Angiogenesis, occurring, e.g., in response to metabolic stress within hypoxic tissues, enhances tissue capillarization. Arteriogenesis denotes the adaptive outgrowth of pre-existent collateral arteries to bypass arterial stenoses in response to hemodynamic changes. It has been debated whether vasculogenesis occurs in the adult, and whether or not circulating progenitor cells structurally contribute to vessel regeneration. Secondly, the major determinants of vascular growth - genetic predisposition, metabolic factors (hypoxia), and hemodynamics - cannot be assigned in a mutually exclusive fashion to vasculogenesis, angiogenesis, and arteriogenesis, respectively; rather, mechanisms overlap. Lastly, all three mechanisms of vessel growth seem to contribute to physiological embryogenesis as well as adult adaptive vascularization as occurs in tumors or to circumvent arterial stenosis. Thus, much conceptual and terminological confusion has been created, while therapies targeting neovascularization have yielded promising results in the lab, but failed randomized studies when taken to the bedside. Therefore, this review article aims at providing an exact definition of the mechanisms of vascular growth and their contribution to embryonic development as well as adult adaptive revascularization. We have been looking for potential reasons for why clinical trials have failed, how vitally the application of appropriate methods of measuring and assessment influences study outcomes, and how relevant, e.g., results gained in models of vascular occlusive disease may be for antineoplastic strategies, advocating a reverse bedside-to-bench approach, which may hopefully yield successful approaches to therapeutically targeting vascular growth.
血管生成是发育过程中第一个功能性器官系统形成的过程，并持续到成年期，在此期间，它通常与疾病状态有关。遗传决定的血管发生在个体发生过程中产生初级血管丛。血管生成，例如，在缺氧组织中的代谢应激下发生，增强组织毛细血管化。动脉生成是指前存在的侧支动脉在血流动力学变化时适应生长，以绕过动脉狭窄。目前仍存在争议的是，血管发生是否发生在成年期，以及循环祖细胞是否在结构上有助于血管再生。其次，血管生长的主要决定因素 - 遗传易感性、代谢因素（缺氧）和血液动力学 - 不能以相互排斥的方式分别分配给血管发生、血管生成和动脉生成；相反，机制是重叠的。最后，三种血管生长机制似乎都有助于生理性胚胎发生以及成年期适应性血管化，如发生在肿瘤中或绕过动脉狭窄。因此，虽然针对新生血管形成的治疗方法在实验室中取得了有希望的结果，但在进行临床试验时却失败了，这造成了概念和术语上的混乱。因此，本文旨在提供血管生长机制的精确定义及其对胚胎发育和成年适应性血管化的贡献。我们一直在寻找临床试验失败的潜在原因，以及适当的测量和评估方法的应用对研究结果的影响至关重要，以及例如，在血管闭塞性疾病模型中获得的结果可能与抗肿瘤策略相关，提倡反向床旁到临床的方法，这可能有希望产生成功的靶向血管生长的治疗方法。
