Boissonneault G A, Hennig B, Ouyang C M
Department of Clinical Sciences, University of Kentucky, Lexington 40536.
Proc Soc Exp Biol Med. 1991 Mar;196(3):338-43. doi: 10.3181/00379727-196-43198.
A spectrum of cholesterol oxidation derivatives (oxysterols) is generated in food products exposed to heat or radiation in the presence of oxygen. One of these derivatives (cholestan-3 beta,5 alpha,6 beta-triol) was shown to compromise the selective barrier function of cultured vascular endothelial cell monolayers, an action that may initiate atherosclerotic lesion formation. This study sought to investigate the relationship of cholesterol synthesis inhibition by several naturally occurring oxysterols to depression of vascular endothelial cell monolayer barrier function, determined as an increase in albumin transfer across cultured endothelial monolayers. All oxysterols tested caused a variable time- and dose-dependent elevation in trans-endothelial albumin transfer, and they were also able to inhibit cholesterol biosynthesis to varying degrees. Pure cholesterol was without effect on both counts. The correlation between the increase in albumin transfer related to oxysterol exposure and the ability of oxysterols to suppress cholesterol biosynthesis was, however, poor. Moreover, mevinolin, a water-soluble competitive inhibitor of cholesterol synthesis, reduced the rate of cholesterol synthesis to 0.9% of control but did not significantly increase albumin transfer. Cholestan-3 beta,5 alpha,6 beta-triol caused a 660% elevation in albumin transfer while cholesterol synthesis remained at 11% of control. We conclude that changes in endothelial barrier function caused by exposure to the oxysterols examined, but not pure cholesterol, are probably related to factors other than the well-known action of cholesterol biosynthesis inhibition. These findings may have implications in the development of atherosclerosis.
在有氧条件下，暴露于热或辐射的食品中会产生一系列胆固醇氧化衍生物（氧化甾醇）。其中一种衍生物（胆甾烷-3β,5α,6β-三醇）已被证明会损害培养的血管内皮细胞单层的选择性屏障功能，这种作用可能引发动脉粥样硬化病变的形成。本研究旨在探讨几种天然存在的氧化甾醇对胆固醇合成的抑制作用与血管内皮细胞单层屏障功能降低之间的关系，通过测量白蛋白跨培养内皮单层的转运增加来确定该屏障功能。所有测试的氧化甾醇均导致跨内皮白蛋白转运呈时间和剂量依赖性的变化，并且它们还能够不同程度地抑制胆固醇生物合成。纯胆固醇对这两项指标均无影响。然而，与氧化甾醇暴露相关的白蛋白转运增加与氧化甾醇抑制胆固醇生物合成的能力之间的相关性较差。此外，胆固醇合成的水溶性竞争性抑制剂美伐他汀将胆固醇合成速率降低至对照的0.9%，但并未显著增加白蛋白转运。胆甾烷-3β,5α,6β-三醇使白蛋白转运增加了660%，而胆固醇合成仍为对照的11%。我们得出结论，暴露于所检测的氧化甾醇而非纯胆固醇所引起的内皮屏障功能变化，可能与胆固醇生物合成抑制这一众所周知的作用之外的其他因素有关。这些发现可能对动脉粥样硬化的发展具有重要意义。
