Interaction of arterial proteoglycans with low density lipoproteins (LDLs): from theory to promising therapeutic approaches

Interaction of arterial proteoglycans with low density lipoproteins (LDLs): from theory to promising therapeutic approaches
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动脉蛋白聚糖与低密度脂蛋白 (LDL) 的相互作用:从理论到有前途的治疗方法

DOI:
10.1016/j.medntd.2019.100016
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发表时间:
2019-09
影响因子:
--
通讯作者:
Deng Xiaoyan
Deng Xiaoyan
中科院分区:
--
文献类型:
--
作者:
Kang Hongyan;Lu Jinyan;Yang Jiali;Fan Yubo;Deng Xiaoyan

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虽然动脉粥样硬化是一个多因素的过程,蛋白多糖介导的脂蛋白(LDL)在内皮下空间的保留是一个必要的和足够的事件,在挑起病变的启动。蛋白聚糖(Proteoglycans,PG)通常由一条或多条糖胺聚糖链(glycosaminoglycan chains,GAG)共价连接而成,主要包括串珠蛋白聚糖(perlecan)、双糖蛋白聚糖(biglycan)、多功能蛋白聚糖(versican)和核心蛋白聚糖(decorin)。LDL和蛋白聚糖之间的相互作用显然是由apoB-100中的碱性氨基酸介导的,apoB-100是LDL的部分,与蛋白聚糖的带负电荷的GAG(硫酸酯或碳水化合物基团)静电相互作用,或者通过一些桥分子如鞘磷脂酶(SMase)或脂蛋白脂肪酶(LpL)。在后面的章节中,我们整理了迄今为止提出的有希望的治疗方法,靶向LDL-PGs相互作用。目前对LDL与PGs相互作用的研究主要集中在细胞外基质(ECM)中的串珠素、双糖蛋白聚糖、核心蛋白聚糖和多功能蛋白聚糖,未来的研究应更多地关注内皮细胞表面糖萼及其与LDL的相互作用,寻找更有针对性的治疗靶点。
Although atherosclerosis is a multifactorial process, proteoglycans mediated lipoprotein (LDL) retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation. Proteoglycans (PGs) are usually composed of one core protein backbone with one or more glycosaminoglycan chains (GAGs) covalently linked, mainly include perlecan, biglycan, versican, and decorin. The interaction between LDL and proteoglycans is apparently mediated by the basic amino acids in apoB-100, the moiety of LDL, electrostatic interacting with the negatively charged GAGs (sulfate or carbohydrate groups) of proteoglycans or though some bridge molecules like sphingomyelinase (SMase) or lipoprotein lipase (LpL). In the later section, we collate the promising therapeutic approaches that have been proposed up to now, targeting LDL-PGs interaction. It should be concluded that previous studies on interaction between LDL and PGs mainly focused on perlecan, biglycan, decorin, and versican that all located in the extracellular matrix (ECM), future studies should pay more attention to the endothelial surface glycocalyx and its interaction with LDLs, seeking promising therapeutic targets more specifically.
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