Macrophages exposed to hypoxia secrete proteoglycans for which LDL has higher affinity
Macrophages exposed to hypoxia secrete proteoglycans for which LDL has higher affinity
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DOI：
10.1016/j.atherosclerosis.2010.12.017
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发表时间：
2011-03-01
期刊：
影响因子：
5.3
通讯作者：
Bondjers, Goran
中科院分区：
文献类型：
--
作者：
Asplund, Annika;Friden, Vincent;Bondjers, Goran
巨噬细胞在动脉粥样硬化病变的缺氧区显著。它们分泌的蛋白聚糖（PG）可以调节脂蛋白的保留以及参与动脉粥样硬化的酶、细胞因子和生长因子的活性。Versican似乎是动脉内膜结合LDL的主要细胞外基质成分之一。我们最近的研究表明，缺氧增加巨噬细胞中versican和perlecan的表达，并且这种增加受缺氧诱导因子（hypoxia inducible factor， HIF）的调节。在这里，我们报道了缺氧对人单核细胞源性巨噬细胞（HMDM）分泌的糖胺聚糖（GAG）的影响及其与LDL的相互作用。暴露于0.5% O(2)（缺氧）24小时后，与21% O(2)（对照细胞）相比，分泌PG的代谢标记GAG对LDL具有更高的亲和力。低氧条件下HMDM分泌的GAG更硫酸化，长度更长，这可能是LDL对这些GAG链的亲和力增加的原因。这些结果表明，缺氧诱导巨噬细胞GAG生物合成的变化对与LDL的相互作用有重要影响。如果在体内存在，GAG与LDL的增强关联可能有助于缺氧内膜动脉粥样硬化的发展。2010爱思唯尔爱尔兰有限公司版权所有。
Macrophages are prominent in hypoxic areas of atherosclerotic lesions. Their secreted proteoglycans (PG) can modulate the retention of lipoproteins as well as the activity of enzymes, cytokines, and growth factors involved in atherogenesis. Versican appears to be one of the main extracellular matrix components binding LDL in the arterial intima. We have recently shown that hypoxia increases versican and perlecan expression in macrophages, and that this increase was regulated by the hypoxia inducible factor (HIF). Here we report effects of hypoxia on human monocyte-derived macrophage (HMDM) secreted glycosaminoglycans (GAG), and its interaction with LDL. After 24 h exposure to 0.5% O(2) (hypoxia), metabolically labeled GAG of secreted PG had higher affinity for LDL compared to 21% O(2) (control cells). GAG secreted by HMDM in hypoxia were found to be more sulfated and longer which might be responsible for the increased affinity of LDL for these GAG chains. These results indicate that hypoxia induced changes in macrophage GAG biosynthesis have important consequences for the interaction with LDL. If present in vivo, an augmented association of GAG with LDL might contribute to the development of atherosclerosis in hypoxic intima. (C) 2010 Elsevier Ireland Ltd. All rights reserved.