Dallinga Marchien G, Dallinga-Thie Geesje M
aDepartment of Ophthalmology bDepartment of Vascular cDepartment of Experimental Vascular Medicine, Academic Medical Center Amsterdam, University of Amsterdam, The Netherlands.
Curr Opin Lipidol. 2016 Apr;27(2):181-6. doi: 10.1097/MOL.0000000000000271.
This article summarizes the current evidence to support a role of sulfatase 2 (SULF2) in triglyceride-rich lipoprotein (TRL) metabolism and angiogenesis.
Heparan sulfate proteoglycans (HSPG) are involved in the hepatic clearance of TRLs in mice and in humans. Different genetically modified mouse models have been instrumental to provide evidence that syndecan1, the core protein of HSPG, but also the degree of sulfation of the heparin sulfate chain, attached to syndecan 1, is important for hepatic TRL metabolism. Studies in humans demonstrate the regulating role of SULF2 in the hepatic uptake of TRL by HSPG and demonstrate the importance of 6-O-sulfation, modulated by SULF2, for HSPG function. The role of SULF2 in angiogenesis is illustrated by increased SULF2 mRNA expression in the stalk cells of angiogenic vascular sprouts that use fatty acids derived from TRL as a source for biomass production. Interestingly, SULF2 also interferes with HSPG-vascular endothelial growth factor binding, which impacts upon the angiogenic properties of stalk cells.
SULF2 is a multifaceted protein involved in TRL homeostasis and angiogenesis. Future investigations should focus on the potential benefits of targeting SULF2 in atherosclerosis and angiogenesis.
本文总结了当前支持硫酸酯酶2（SULF2）在富含甘油三酯脂蛋白（TRL）代谢和血管生成中作用的证据。
硫酸乙酰肝素蛋白聚糖（HSPG）参与小鼠和人类肝脏中TRL的清除。不同的基因修饰小鼠模型有助于提供证据表明，HSPG的核心蛋白syndecan1以及连接在syndecan 1上的硫酸乙酰肝素链的硫酸化程度对肝脏TRL代谢很重要。对人类的研究表明SULF2在HSPG介导的肝脏摄取TRL中的调节作用，并证明由SULF2调节的6-O-硫酸化对HSPG功能的重要性。在利用源自TRL的脂肪酸作为生物质生产来源的血管生成性血管芽的茎细胞中，SULF2 mRNA表达增加，这说明了SULF2在血管生成中的作用。有趣的是，SULF2还干扰HSPG与血管内皮生长因子的结合，这会影响茎细胞的血管生成特性。
SULF2是一种参与TRL稳态和血管生成的多面蛋白。未来的研究应聚焦于靶向SULF2在动脉粥样硬化和血管生成方面的潜在益处。
