Dulak Józef, Łoboda Agnieszka, Zagórska Anna, Józkowicz Alicja
Department of Cell Biochemistry, Faculty of Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
Antioxid Redox Signal. 2004 Oct;6(5):858-66. doi: 10.1089/ars.2004.6.858.
Angiogenesis occurring during reparative or pathological processes is driven by various inflammatory mediators that influence the synthesis of growth factors. It has been recognized recently that reactive oxygen species (ROS) and nitric oxide (NO) are important modulators of the synthesis and activity of vascular endothelial growth factor (VEGF), a major angiogenic molecule. Moreover, heme oxygenase-1 (HO-1), a ubiquitous stress-inducible enzyme that is induced by ROS and NO, was recently discovered to be involved in angiogenesis. Genetic overexpression of HO-1 enhanced VEGF synthesis and augmented formation of vascular capillaries, improving the blood flow in ischemic tissues. In addition, by-products of HO-1 exert numerous effects that can also influence angiogenesis in both positive and negative ways. Therefore, the antiinflammatory effects of HO-1 can attenuate the excess formation of blood vessels in inflammatory angiogenesis. In this review, the recent data on the role of HO-1 in angiogenesis are critically discussed. It is suggested that further studies using potent and specific augmentation of HO-1 gene expression by viral vectors, as well as targeted, specific inhibition of HO-1 expression, are required to elucidate fully the complex role of this enzymatic pathway in angiogenesis.
修复或病理过程中发生的血管生成由多种影响生长因子合成的炎症介质驱动。最近人们认识到，活性氧（ROS）和一氧化氮（NO）是血管内皮生长因子（VEGF，一种主要的血管生成分子）合成和活性的重要调节因子。此外，血红素加氧酶-1（HO-1）是一种普遍存在的应激诱导酶，可由ROS和NO诱导产生，最近发现它参与血管生成。HO-1的基因过表达增强了VEGF的合成并增加了血管毛细血管的形成，改善了缺血组织中的血流。此外，HO-1的副产物发挥着许多也能以正负两种方式影响血管生成的作用。因此，HO-1的抗炎作用可减弱炎症性血管生成中血管的过度形成。在本综述中，对HO-1在血管生成中作用的最新数据进行了批判性讨论。建议需要进一步开展研究，通过病毒载体有效且特异性地增强HO-1基因表达，以及对HO-1表达进行靶向、特异性抑制，以充分阐明该酶促途径在血管生成中的复杂作用。
