School of Pharmacy, The University of Queensland, Brisbane, Queensland, 4102, Australia; Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, 4111, Australia; Discovery Biology, School of Environment and Science, Griffith University, Nathan, Queensland, 4111, Australia.
Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, 4111, Australia; Discovery Biology, School of Environment and Science, Griffith University, Nathan, Queensland, 4111, Australia.
Atherosclerosis. 2024 Oct;397:118552. doi: 10.1016/j.atherosclerosis.2024.118552. Epub 2024 Aug 7.
The subendothelial retention of circulating lipoproteins on extracellular matrix proteins and proteoglycans is one of the earliest events in the development of atherosclerosis. Multiple factors, including the size, type, composition, surrounding pH, and chemical modifications to lipoproteins, influence the electrostatic interactions between relevant moieties of the apolipoproteins on lipoproteins and the glycosaminoglycans of proteoglycans. The length and chemical composition of glycosaminoglycan chains attached to proteoglycan core proteins determine the extent of initial lipoprotein binding and retention in the artery wall. The phenomena of hyperelongation of glycosaminoglycan chains is associated with initial lipid retention and later atherosclerotic plaque formation. This review includes a summary of the current literature surrounding cellular mechanisms leading to GAG chain modification and lipid retention and discusses potential therapeutic strategies to target lipoprotein:proteoglycan interactions to prevent the development and progression of atherosclerosis.
循环脂蛋白在细胞外基质蛋白和蛋白聚糖上的亚内皮滞留是动脉粥样硬化发展的最早事件之一。多种因素，包括脂蛋白的大小、类型、组成、周围 pH 值以及化学修饰，都会影响脂蛋白载脂蛋白相关部分与蛋白聚糖糖胺聚糖之间的静电相互作用。连接到蛋白聚糖核心蛋白上的糖胺聚糖链的长度和化学组成决定了初始脂蛋白结合和在动脉壁中滞留的程度。糖胺聚糖链的超延长现象与最初的脂质滞留和随后的动脉粥样硬化斑块形成有关。这篇综述包括对目前围绕导致 GAG 链修饰和脂质滞留的细胞机制的文献的总结，并讨论了针对脂蛋白-蛋白聚糖相互作用的潜在治疗策略，以预防动脉粥样硬化的发生和发展。
