Ribatti Domenico, Conconi Maria Teresa, Nussdorfer Gastone G
Department of Human Anatomy and Histology, School of Medicine, University of Bari, Bari, Italy.
Pharmacol Rev. 2007 Jun;59(2):185-205. doi: 10.1124/pr.59.2.3.
Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro proangiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG-II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide-Y, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF (ANG-II, ETs, PAMP, resistin, VIP and PACAP) and/or FGF-2 systems (PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF-2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis.
血管生成是指新血管从已有的血管中形成的过程，它受多种“经典”因子调控，其中研究最多的是血管内皮生长因子（VEGF）和成纤维细胞生长因子-2（FGF-2）。近年来，研究表明，除了经典因子外，许多内源性肽在血管生成中也发挥着重要的调节作用。这些调节肽各自具有众所周知的特定生物学活性，它们与其受体一起存在于血管中，并可能参与“血管生成开关”的控制。促红细胞生成素、血管紧张素II（ANG-II）、内皮素（ETs）、肾上腺髓质素（AM）、肾上腺髓质素前体N端20肽（PAMP）、尾加压素II、瘦素、脂联素、抵抗素、神经肽Y、血管活性肠肽（VIP）、垂体腺苷酸环化酶激活多肽（PACAP）和P物质已被证明在体内和体外具有促血管生成作用。有证据表明，其中一些肽的血管生成作用至少部分是通过它们对VEGF（ANG-II、ETs、PAMP、抵抗素、VIP和PACAP）和/或FGF-2系统（PAMP和瘦素）的刺激作用介导的。AM可提高内皮细胞中VEGF的表达，但VEGF阻断并不影响AM的促血管生成作用。其他内源性肽据报道在体内和体外具有抗血管生成作用。这些包括抑制VEGF系统的生长抑素和利钠肽，以及拮抗FGF-2作用的胃饥饿素。对血管生成“非经典”调节因子进行研究可能为与血管生成失调相关疾病的治疗开辟新的前景。
