Boissonneault G A, Hennig B, Wang Y, Ouyang C M, Krahulik K, Cunnup L, Oeltgen P R
Department of Clinical Sciences, University of Kentucky, Lexington.
Ann Nutr Metab. 1991;35(4):226-32. doi: 10.1159/000177650.
High levels of plasma low-density lipoproteins (LDL) are known to be a risk factor for developing coronary artery disease although the specific mechanism involved is unknown. It may be related to effects of oxidized lipid components of LDL on vascular endothelial barrier function (EBF). This study addressed the hypothesis that LDL-associated products of cholesterol oxidation, oxysterols, decrease EBF resulting in increased penetration of blood components such as LDL into the arterial wall. LDL from human volunteers and rabbits was enriched with cholesterol or cholestan-3 beta,5 alpha,6 beta triol (Triol) by in vitro incubation. Exposure of cultured vascular endothelial cell monolayers to LDL enriched with Triol reduced EBF, measured as an increase in transendothelial albumin transfer, whereas cholesterol enrichment, like un-enriched LDL, had no effect on EBF. In a second experimental series, rabbits were gavaged with 100 mg of cholesterol or Triol/kg body weight, and LDL was isolated from serum 24 h after gavage. As was seen with the in vitro experiments, Triol-enriched LDL markedly decreased EBF. Similarly, LDL from cholesterol-gavaged rabbits reduced EBF, while LDL from vehicle treated rabbits had no effect. These results suggest that LDL-associated oxysterols are detrimental to normal barrier function of the vascular endothelium. Disruption of this barrier function may serve as an initiating factor in atherosclerotic lesion formation.
高水平的血浆低密度脂蛋白（LDL）是已知的冠状动脉疾病发生的危险因素，尽管其中涉及的具体机制尚不清楚。这可能与LDL氧化脂质成分对血管内皮屏障功能（EBF）的影响有关。本研究探讨了这样一个假设：LDL相关的胆固醇氧化产物，即氧甾醇，会降低EBF，导致诸如LDL等血液成分进入动脉壁的渗透率增加。通过体外孵育，将来自人类志愿者和兔子的LDL用胆固醇或胆甾烷-3β,5α,6β-三醇（三醇）进行富集。将培养的血管内皮细胞单层暴露于富含三醇的LDL中会降低EBF，以跨内皮白蛋白转运增加来衡量，而胆固醇富集，与未富集的LDL一样，对EBF没有影响。在第二个实验系列中，给兔子灌胃100mg/kg体重的胆固醇或三醇，灌胃24小时后从血清中分离LDL。正如体外实验所见，富含三醇的LDL显著降低EBF。同样，来自灌胃胆固醇的兔子的LDL降低了EBF，而来自用赋形剂处理的兔子的LDL则没有影响。这些结果表明，LDL相关的氧甾醇对血管内皮的正常屏障功能有害。这种屏障功能的破坏可能是动脉粥样硬化病变形成的起始因素。
