Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. To investigate whether these hypercholesterolemic effects on the skin also occur in hyperalphalipoproteinemia, we compared skins of wild-type and SR-BI knockout (SR-BI-/-) mice. SR-BI deficiency did not affect the epidermal cholesterol content and induced only minor changes in the ceramide subclasses. The epidermal free fatty acid (FFA) pool was, however, enriched in short and unsaturated chains. Plasma CE levels strongly correlated with epidermal FFA C18:1 content. The increase in epidermal FFA coincided with downregulation of cholesterol and FFA synthesis genes, suggesting a compensatory response to increased flux of plasma cholesterol and FFAs into the skin. Importantly, the SR-BI-/- epidermal lipid barrier showed increased permeability to ethyl-paraminobenzoic acid, indicating an impairment of the barrier function. In conclusion, increased HDL-cholesterol levels in SR-BI-/- mice can alter the epidermal lipid composition and lipid barrier function similarly as observed in hypercholesterolemia due to elevated levels of apoB-containing lipoproteins.

中文翻译：

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高脂蛋白血症清除剂受体BI基因敲除小鼠表现出破坏的表皮脂质屏障。

I类清道夫受体B（SR-BI）介导高密度脂蛋白（HDL）对胆固醇酯（CE）的选择性摄取。SR-BI功能受损会导致高脂蛋白血症，而高密度脂蛋白部分中胆固醇的转运水平升高。研究表明，含载脂蛋白B（apoB）的脂蛋白中胆固醇的积累会改变皮肤脂质的组成和屏障功能。为了研究这些高胆固醇血症对皮肤的作用是否也发生在高α脂蛋白血症中，我们比较了野生型和SR-BI基因敲除（SR-BI-/-）小鼠的皮肤。SR-BI缺乏症不会影响表皮胆固醇含量，只会引起神经酰胺亚类的微小变化。但是，表皮游离脂肪酸（FFA）库富含短链和不饱和链。血浆CE水平与表皮FFA C18：1含量密切相关。表皮FFA的增加与胆固醇和FFA合成基因的下调相吻合，表明对血浆胆固醇和FFA进入皮肤的通量增加的补偿性反应。重要的是，SR-BI-/-表皮脂质屏障显示出对乙基-对氨基苯甲酸的渗透性增加，表明屏障功能受损。总之，由于高水平的含apoB的脂蛋白，在SR-BI-/-小鼠中增加的HDL-胆固醇水平可以改变表皮脂质组成和脂质屏障功能，与在高胆固醇血症中观察到的相似。提示对血浆胆固醇和FFA进入皮肤的通量增加有补偿性反应。重要的是，SR-BI-/-表皮脂质屏障显示出对乙基-对氨基苯甲酸的渗透性增加，表明屏障功能受损。总之，由于高水平的含apoB的脂蛋白，在SR-BI-/-小鼠中增加的HDL-胆固醇水平可以改变表皮脂质组成和脂质屏障功能，与高胆固醇血症相似。提示对血浆胆固醇和FFA进入皮肤的通量增加有补偿性反应。重要的是，SR-BI-/-表皮脂质屏障显示出对乙基-对氨基苯甲酸的渗透性增加，表明屏障功能受损。总之，由于高水平的含apoB的脂蛋白，在SR-BI-/-小鼠中增加的HDL-胆固醇水平可以改变表皮脂质组成和脂质屏障功能，与在高胆固醇血症中观察到的相似。