Sima Anca V, Stancu Camelia S, Simionescu Maya
Institute of Cellular Biology and Pathology Nicolae Simionescu, 8 B.P.Hasdeu Street, 050568 Bucharest, Romania.
Cell Tissue Res. 2009 Jan;335(1):191-203. doi: 10.1007/s00441-008-0678-5. Epub 2008 Sep 17.
Their strategic location between blood and tissue and their constitutive properties allow endothelial cells (EC) to monitor the transport of plasma molecules, by employing bidirectional receptor-mediated and receptor-independent transcytosis and endocytosis, and to regulate vascular tone, cellular cholesterol and lipid homeostasis. These cells are also involved in signal transduction, immunity, inflammation and haemostasis. Cardiovascular risk factors, such as hyperlipaemia/dyslipidaemia trigger the molecular machinery of EC to respond to insults by modulation of their constitutive functions followed by dysfunction and ultimately by injury and apoptosis. The gradual activation of EC consists initially in the modulation of two constitutive functions: (1) permeability, i.e. increased transcytosis of lipoproteins, and (2) biosynthetic activity, i.e. enhanced synthesis of the basement membrane and extracellular matrix. The increased transcytosis and the reduced efflux of beta-lipoproteins (betaLp) lead to their retention within the endothelial hyperplasic basal lamina as modified lipoproteins (MLp) and to their subsequent alteration (oxidation, glycation, enzymatic modifications). MLp generate chemoattractant and inflammatory molecules, triggering EC dysfunction (appearance of new adhesion molecules, secretion of chemokines, cytokines), characterised by monocyte recruitment, adhesion, diapedesis and residence within the subendothelium. In time, EC in the athero-prone areas alter their net negative surface charge, losing their non-thrombogenic ability, become loaded with lipid droplets and turn into foam cells. Prolonged and/or repeated exposure to cardiovascular risk factors can ultimately exhaust the protective effect of the endogenous anti-inflammatory system within EC. As a consequence, EC may progress to senescence, lose their integrity and detach into the circulation.
它们位于血液与组织之间的关键位置以及其固有特性，使得内皮细胞（EC）能够通过双向受体介导的和不依赖受体的转胞吞作用及内吞作用来监测血浆分子的运输，并调节血管张力、细胞胆固醇及脂质稳态。这些细胞还参与信号转导、免疫、炎症和止血过程。心血管危险因素，如高脂血症/血脂异常，会触发内皮细胞的分子机制，通过调节其固有功能来应对损伤，随后功能失调，最终导致损伤和凋亡。内皮细胞的逐渐激活最初表现为两种固有功能的调节：（1）通透性，即脂蛋白转胞吞作用增加；（2）生物合成活性，即基底膜和细胞外基质合成增强。转胞吞作用增加以及β - 脂蛋白（βLp）外流减少，导致它们作为修饰脂蛋白（MLp）保留在内皮增生的基底膜内，并随后发生改变（氧化、糖基化、酶促修饰）。MLp产生趋化因子和炎症分子，触发内皮细胞功能障碍（新黏附分子的出现、趋化因子和细胞因子的分泌），其特征为单核细胞募集、黏附、穿内皮迁移并在内皮下停留。随着时间推移，易发生动脉粥样硬化区域的内皮细胞改变其净负表面电荷，失去其抗血栓形成能力，充满脂滴并转变为泡沫细胞。长期和/或反复暴露于心血管危险因素最终可能耗尽内皮细胞内源性抗炎系统的保护作用。结果，内皮细胞可能会进入衰老状态，失去其完整性并脱落进入循环系统。
