Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, New South Wales, Australia.
Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2089-98. doi: 10.1161/ATVBAHA.110.209643. Epub 2010 Aug 26.
Although there have been a multitude of studies, the mechanisms of angiogenesis remain incompletely understood. Increasing evidence suggests that cellular redox homeostasis is an important regulator of angiogenesis. The thioredoxin (TRX) system functions as an endogenous antioxidant that can exert influence over endothelial cell function via modulation of cellular redox status. It has become apparent that the cytosolic TRX1 isoform participates in both canonical and novel angiogenic signaling pathways and may represent an avenue for therapeutic exploitation. Recent studies have further identified a role for the mitochondrial isoform TRX2 in ischemia-induced angiogenesis. TRX-interacting protein (TXNIP) is the endogenous inhibitor of TRX redox activity that has been implicated in growth factor-mediated angiogenesis. As TXNIP is strongly induced by glucose, this molecule could be of consequence to disordered angiogenesis manifest in diabetes mellitus. This review will focus on data implicating the TRX system in endothelial cell homeostasis and angiogenesis.
尽管已经有大量的研究，但血管生成的机制仍不完全清楚。越来越多的证据表明，细胞内氧化还原稳态是血管生成的一个重要调节剂。硫氧还蛋白（TRX）系统作为一种内源性抗氧化剂，可以通过调节细胞内氧化还原状态来影响内皮细胞功能。目前已经很明显，细胞质 TRX1 同工型参与了经典和新型血管生成信号通路，并可能成为治疗靶点。最近的研究进一步确定了线粒体同工型 TRX2 在缺血诱导的血管生成中的作用。TRX 相互作用蛋白（TXNIP）是 TRX 氧化还原活性的内源性抑制剂，它与生长因子介导的血管生成有关。由于 TXNIP 受到葡萄糖的强烈诱导，因此这种分子可能与糖尿病中表现出的血管生成紊乱有关。这篇综述将重点介绍 TRX 系统在内皮细胞稳态和血管生成中的作用。
