Detergent-mediated phospholipidation of plasma lipoproteins increases HDL cholesterophilicity and cholesterol efflux via SR-BI
Detergent-mediated phospholipidation of plasma lipoproteins increases HDL cholesterophilicity and cholesterol efflux via SR-BI
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DOI：
10.1021/bi0608717
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发表时间：
2006-09-26
期刊：
影响因子：
2.9
通讯作者：
Pownall, Henry J.
中科院分区：
文献类型：
--
作者：
Pownall, Henry J.
细胞胆固醇外流是胆固醇逆向转运的早期必需步骤，这是一种假定的抗动脉粥样硬化机制，人类血浆高密度脂蛋白(HDL)通过这种机制将胆固醇从外周组织输送到肝脏，以便循环或处置。高密度脂蛋白-磷脂含量是脂蛋白中与胆固醇结合的基本成分，因此是胆固醇外流的主要决定因素。因此，增加脂蛋白的磷脂化，特别是高密度脂蛋白，是增加胆固醇外流的一种策略。本研究验证了一种简单的、新的血浆脂蛋白磷脂微扰法；我们定量了人血浆脂蛋白的亲脂性，以及脂蛋白磷脂对亲胆固醇和通过B型清道夫受体(SR-BI)介导的细胞胆固醇流出的影响。我们确定低密度脂蛋白比高密度脂蛋白更亲胆固醇，低密度脂蛋白对磷脂的亲和力比高密度脂蛋白高，而高密度脂蛋白的磷脂容量比低密度脂蛋白高。人血浆总脂蛋白的磷脂化增强了胆固醇的外流，这种作用主要是通过高密度脂蛋白的优先磷脂化来实现的。我们的结论是，增加高密度脂蛋白磷脂增加了它的亲胆固醇活性，从而使它成为细胞胆固醇外流的更好的受体。通过洗涤剂扰动脂蛋白的磷脂是一种简单的方法，可以增加高密度脂蛋白的亲脂性和胆固醇外流，这种方法可能在临床上有用。
Cellular cholesterol efflux is an early, obligatory step in reverse cholesterol transport, the putative antiatherogenic mechanism by which human plasma high-density lipoproteins (HDL) transport cholesterol from peripheral tissue to the liver for recycling or disposal. HDL-phospholipid content is the essential cholesterol-binding component of lipoproteins and therefore a major determinant of cholesterol efflux. Thus, increased phospholipidation of lipoproteins, particularly HDL, is one strategy for increasing cholesterol efflux. This study validates a simple, new detergent perturbation method for the phospholipidation of plasma lipoproteins; we have quantified the cholesterophilicity of human plasma lipoproteins and the effects of lipoprotein phospholipidation on cholesterophilicity and cellular cholesterol efflux mediated by the class B type I scavenger receptor (SR-BI). We determined that low-density lipoproteins (LDL) are more cholesterophilic than HDL and that LDL has a higher affinity for phospholipids than HDL whereas HDL has a higher phospholipid capacity than LDL. Phospholipidation of total human plasma lipoproteins enhances cholesterol efflux, an effect that occurs largely through the preferential phospholipidation of HDL. We conclude that increasing HDL phospholipid increases its cholesterophilicity, thereby making it a better acceptor of cellular cholesterol efflux. Phospholipidation of lipoproteins by detergent perturbation is a simple way to increase HDL cholesterophilicity and cholesterol efflux in a way that may be clinically useful.