Nielsen L B
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.
Atherosclerosis. 1996 Jun;123(1-2):1-15. doi: 10.1016/0021-9150(96)05802-9.
The aim of the review is to summarize the present knowledge on determinants of transfer of low density lipoprotein (LDL) into the arterial wall, particularly in relation to the risk of development of atherosclerosis. The flux of LDL into the arterial wall (in moles of LDL per surface area per unit of time) has two major determinants, i.e. the LDL concentration in plasma and the arterial wall permeability. LDL enters the arterial wall as intact particles by vesicular ferrying through endothelial cells and/or by passive sieving through pores in or between endothelial cells. Estimates in vivo of the LDL permeability of a normal arterial wall vary between 5 and 100 nl/cm2/h. In laboratory animals, the regional variation in the arterial wall permeability predicts the pattern of subsequent dietary induced atherosclerosis. Moreover, mechanical or immunological injury of the arterial wall increases the LDL permeability and is accompanied by accelerated development of experimental atherosclerosis. This supports the idea that an increased permeability to LDL, like an increased plasma LDL concentration, increases the risk of atherosclerosis. Hypertension, smoking, genetic predisposition, atherosclerosis, and a small size of LDL may all increase the arterial wall permeability to LDL and in this way increase the risk of accelerated development of atherosclerosis. The hypothesis that atherosclerosis risk can be reduced by improving the barrier function of the arterial wall towards the entry of LDL remains to be investigated; agents which directly modulate the LDL permeability of the arterial wall in vivo await identification.
本综述的目的是总结目前关于低密度脂蛋白（LDL）转运至动脉壁的决定因素的知识，特别是与动脉粥样硬化发生风险相关的因素。LDL进入动脉壁的通量（每单位时间每表面积的LDL摩尔数）有两个主要决定因素，即血浆中LDL浓度和动脉壁通透性。LDL作为完整颗粒通过内皮细胞的囊泡转运和/或通过内皮细胞内或之间的孔隙被动筛分进入动脉壁。正常动脉壁LDL通透性的体内估计值在5至100 nl/cm²/h之间。在实验动物中，动脉壁通透性的区域差异可预测随后饮食诱导的动脉粥样硬化模式。此外，动脉壁的机械或免疫损伤会增加LDL通透性，并伴随着实验性动脉粥样硬化的加速发展。这支持了这样一种观点，即LDL通透性增加，如同血浆LDL浓度增加一样，会增加动脉粥样硬化的风险。高血压、吸烟、遗传易感性、动脉粥样硬化以及小尺寸的LDL都可能增加动脉壁对LDL的通透性，从而增加动脉粥样硬化加速发展的风险。通过改善动脉壁对LDL进入的屏障功能来降低动脉粥样硬化风险的假说仍有待研究；在体内直接调节动脉壁LDL通透性的药物有待确定。
