Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated?
Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated?
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DOI：
10.1172/jci119377
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发表时间：
1997-05-01
影响因子：
15.9
通讯作者：
Zhang, LJ
中科院分区：
文献类型：
--
作者：
Rosenberg, RD;Shworak, NW;Zhang, LJ
心血管系统的细胞表面和周围细胞外基质含有大量硫酸乙酰肝素蛋白聚糖（HSPG）1（1）。这些高度带电的大分子由不同的核心蛋白组成，这些核心蛋白具有共价连接的不同单糖序列的硫酸乙酰肝素链（HS），这些单糖序列是生物过程的关键介质（2，3）。例如，这些组分参与调节中胚层细胞命运、心脏定位、缺血性损伤后的血管发生和血管生成、细胞与粘附蛋白和血管的相互作用、动脉粥样硬化形成期间平滑肌细胞的增殖、脂蛋白的代谢、内皮细胞的非血栓形成特性等。（4 - 9）。在过去的十年中，详细的研究已经确定了HSPG的结构，揭示了这些组分执行其不同功能的分子机制，并揭示了HS与生物靶标相互作用所需的特定单糖序列。在这篇综述中，我们概述了我们的知识的结构和HSPGs的生物合成的现状，以及描述这些组件与生长因子，酶和蛋白酶抑制剂的相互作用。这些观察结果为阐明HSPGs在其他生物系统中的作用提供了一个概念框架。
The cell surfaces and surrounding extracellular matrix of the cardiovascular system possess large quantities of heparan sulfate proteoglycans (HSPGs) 1 (1). These highly charged macromolecules consist of different core proteins with covalently linked heparan sulfate chains (HS) of varying monosaccharide sequence which serve as critical mediators of biologic processes (2, 3). For example, these components are involved in regulating mesodermal cell fate, positioning of the heart, vasculogenesis and angiogenesis after ischemic injury, interactions of cells with adhesive proteins and blood vessels, proliferation of smooth muscle cells during atherogenesis, metabolism of lipoproteins, nonthrombogenic characteristics of endothelial cells, etc.(4–9). Detailed investigations over the past decade have defined the structures of HSPGs, uncovered the molecular mechanisms by which these components carry out their diverse functions, and revealed that specific monosaccharide sequences of HS are required for interaction with biologic targets. In this review, we outline the current state of our knowledge about the structure and the biosynthesis of HSPGs as well as describe interactions of these components with growth factors, enzymes, and protease inhibitors. These observations provide a conceptual framework for elucidating the roles of HSPGs in other biologic systems.