Hypoxia-induced angiogenesis: good and evil.
Hypoxia-induced angiogenesis: good and evil.
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DOI：
10.1177/1947601911423654
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发表时间：
2011-12-01
期刊：
影响因子：
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通讯作者：
Simon, M Celeste
中科院分区：
文献类型：
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作者：
Krock, Bryan L;Skuli, Nicolas;Simon, M Celeste
血管网络将氧气（O(2)）和营养物质输送到体内的所有细胞。因此，O(2)可用性作为这个复杂器官的主要调节因子就不足为奇了。大多数对低氧(2)的转录反应是由缺氧诱导因子（hif）介导的，这是一种高度保守的转录因子，控制着许多血管生成、代谢和细胞周期基因的表达。因此，HIF通路目前被视为血管生成的主要调节因子。HIF调节可以为多种病理提供治疗益处，包括癌症、缺血性心脏病、外周动脉疾病、伤口愈合和新生血管性眼病。缺氧通过上调多种促血管生成途径促进血管生长，这些途径介导内皮、基质和血管支持细胞生物学的关键方面。有趣的是，最近的研究表明，缺氧影响血管生成的其他方面，包括血管模式、成熟和功能。通过广泛的研究，缺氧和HIF信号在人类疾病中的整体作用越来越清楚。因此，深入了解缺氧如何通过多种细胞类型中不断扩大的途径调节血管生成，对于确定新的治疗靶点和模式至关重要。
The vascular network delivers oxygen (O(2)) and nutrients to all cells within the body. It is therefore not surprising that O(2) availability serves as a primary regulator of this complex organ. Most transcriptional responses to low O(2) are mediated by hypoxia-inducible factors (HIFs), highly conserved transcription factors that control the expression of numerous angiogenic, metabolic, and cell cycle genes. Accordingly, the HIF pathway is currently viewed as a master regulator of angiogenesis. HIF modulation could provide therapeutic benefit for a wide array of pathologies, including cancer, ischemic heart disease, peripheral artery disease, wound healing, and neovascular eye diseases. Hypoxia promotes vessel growth by upregulating multiple pro-angiogenic pathways that mediate key aspects of endothelial, stromal, and vascular support cell biology. Interestingly, recent studies show that hypoxia influences additional aspects of angiogenesis, including vessel patterning, maturation, and function. Through extensive research, the integral role of hypoxia and HIF signaling in human disease is becoming increasingly clear. Consequently, a thorough understanding of how hypoxia regulates angiogenesis through an ever-expanding number of pathways in multiple cell types will be essential for the identification of new therapeutic targets and modalities.