Srinivasan S R, Radhakrishnamurthy B, Vijayagopal P, Berenson G S
Department of Medicine, Louisiana State University School of Medicine, New Orleans 70112.
Adv Exp Med Biol. 1991;285:373-81. doi: 10.1007/978-1-4684-5904-3_45.
The arterial wall proteoglycans play a crucial role in the pathogenesis of atherosclerosis as depicted schematically in Figure 7. Plasma components including lipoproteins cross the endothelium mainly by a non-specific bulk-phase vesicular transport. A selective interaction of apoB-containing lipoproteins occurs with proteoglycans of the subendothelial layer which results in extracellular retention and accumulation of lipoproteins. Such interaction alters the structural and charge characteristics of LDL particles. These altered LDL are taken up by monocyte-derived macrophages by scavenger receptor-mediated endocytosis, leading to cholesteryl ester accumulation and foam cell formation. Further, retention of LDL by proteoglycans in the extracellular matrix also increases the chances of oxidative modification of lipoproteins. All of these changes may be occurring at a marginal level as a normal adaptive process of the arterial wall. However, focal response to chronic hemodynamic stress, hyperlipidemia or other forms of injury may functionally alter the endothelium, and cause greater influx of lipoproteins and smooth muscle cell proliferation, resulting in increased synthesis of proteoglycans with altered characteristics. Enhanced binding of apo-B containing lipoproteins to proteoglycans under these conditions sets the stage for the development of athersclerosis.
如图7示意性所示，动脉壁蛋白聚糖在动脉粥样硬化的发病机制中起关键作用。包括脂蛋白在内的血浆成分主要通过非特异性的整体相囊泡运输穿过内皮。含载脂蛋白B的脂蛋白与内皮下层的蛋白聚糖发生选择性相互作用，导致脂蛋白在细胞外潴留和积聚。这种相互作用改变了低密度脂蛋白颗粒的结构和电荷特性。这些改变的低密度脂蛋白被单核细胞衍生的巨噬细胞通过清道夫受体介导的内吞作用摄取，导致胆固醇酯积聚和泡沫细胞形成。此外，蛋白聚糖将低密度脂蛋白保留在细胞外基质中也增加了脂蛋白氧化修饰的机会。所有这些变化可能作为动脉壁的正常适应性过程在边缘水平发生。然而，对慢性血流动力学应激、高脂血症或其他形式损伤的局灶性反应可能在功能上改变内皮，并导致更多的脂蛋白流入和平滑肌细胞增殖，从而导致合成具有改变特性的蛋白聚糖增加。在这些条件下，含载脂蛋白B的脂蛋白与蛋白聚糖的结合增强为动脉粥样硬化的发展奠定了基础。
