Regulation of vascular endothelial growth factor by hypoxia and its modulation by the von Hippel-Lindau tumor suppressor gene
Regulation of vascular endothelial growth factor by hypoxia and its modulation by the von Hippel-Lindau tumor suppressor gene
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DOI：
10.1038/ki.1997.82
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发表时间：
1997-02-01
影响因子：
19.6
通讯作者：
Goldberg, MA
中科院分区：
文献类型：
--
作者：
Levy, AP;Levy, NS;Goldberg, MA
适应降低的氧张力是所有生物体的基本要求。在高等生物中，对组织供氧减少的两种适应性反应是呼吸频率的增加和红细胞量的增加。这些生理适应分别通过颈动脉体和肾脏中的特定氧传感细胞实现。在分子水平上，这种对缺氧的适应涉及对缺氧应答基因如酪氨酸羟化酶和促红细胞生成素（Epo）的特异性调节。新血管形成或血管生成也是对细胞和组织缺氧的适应性反应[1]。事实上，在冠状动脉疾病中观察到的心脏冠状动脉侧支循环增加、肿瘤生长和转移所需的肿瘤血管生成以及糖尿病视网膜病变被认为是对缺氧的反应[2-4]。血管内皮生长因子（VEGF），也称为血管通透性因子，是一种有效的血管生成因子和内皮细胞特异性有丝分裂原[5，6]，在体外和体内受缺氧调节[1]。此外，与许多肿瘤相关的新生血管反应以及实验诱导的视网膜病变可以用VEGF的中和抗血清抑制[4，7]。因此，VEGF似乎是体内缺氧诱导的血管生成的重要介质。本文综述了我们和其他人对低氧诱导VEGF机制的研究。
Adaptation to decreased oxygen tension is a fundamental requirement of all living organisms. Two well understood adap-tations in higher organisms to a decrease in oxygen delivery to the tissues are an increase in respiratory rate and an increase in red blood cell mass. These physiological adaptations are achieved by specific oxygen sensing cells in the carotid body and kidney, respectively. At a molecular level this adaptation to hypoxia involves the specific regulation of hypoxia responsive genes such as tyrosine hydroxylase and erythropoietin (Epo). New blood vessel formation or angiogenesis is also an adaptive response to cell and tissue hypoxia [1]. Indeed, the increased coronary collateral circulation of the heart seen in coronary artery disease, tumor angiogenesis that is required for tumor growth and metastasis, and diabetic retinopathy are recognized as responses to hypoxia [2—4]. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent angiogenic factor and endothelial cell-specific mitogen [5, 6] that is regulated by hypoxia in vitro and in vivo [1]. Furthermore, the neovascular response associated with many tumors as well as experimentally induced retinopathy can be inhibited with neutralizing antiserum to VEGF [4, 7]. VEGF thus appears to be an important mediator of hypoxia induced angiogenesis in vivo. This review will describe studies that we and others have performed investigating the mechanism of hypoxic induction of VEGF.