Takeuchi N, Saheki S
Department of Laboratory and Clinical Medicine, Ehime University Medical School.
Rinsho Byori. 1995 Aug;43(8):753-62.
Low density lipoprotein (LDL) has been recognized commonly as an atherogenic lipoprotein. Especially, small dense LDL is considered to be more atherogenic than large buoyant LDL. It is contained in polydisperse LDL with various sizes and densities. Although the causative mechanism of LDL heterogeneity has not been elucidated clearly yet, it is supposed to be derived from the heterogeneous mechanism of metabolic processing of the VLDL(very low density lipoprotein)-LDL cascade different from the common pathway. It might be due to quantitative and qualitative abnormalities of secreted VLDL, different susceptibilities to lipoprotein lipase as well as hepatic lipase, and the change of receptor binding abilities of LDL. The development of polydisperse LDL has a genetic background. However, it must be influenced by some environmental factors, since the heterogeneity of LDL is restored completely to a normal monodisperse pattern concomitantly with the decreased serum triglyceride level by dietary caloric restriction. LDL is well known to be oxidized or glycated spontaneously in vivo and in vitro. Such modified LDL loses the binding affinity to the classical LDL receptor and is taken up by monocyte-derived macrophages through scavenger receptors. Since the scavenger receptor system is not down regulated, it promotes the formation of foam cells in the arterial wall accumulating cholesterol and other lipids by excess LDL uptake. Small dense LDL is considered to be easily oxidized or glycated compared with large buoyant LDL. Therefore, it might increase further the atherogenic potency by such modifications.
低密度脂蛋白（LDL）通常被认为是一种致动脉粥样硬化的脂蛋白。特别是，小而密的LDL被认为比大而轻的LDL更具致动脉粥样硬化性。它存在于具有各种大小和密度的多分散LDL中。尽管LDL异质性的致病机制尚未完全阐明，但推测它源自与常见途径不同的极低密度脂蛋白（VLDL）-LDL级联代谢加工的异质性机制。这可能是由于分泌的VLDL在数量和质量上的异常、对脂蛋白脂肪酶以及肝脂肪酶的不同敏感性，以及LDL受体结合能力的改变。多分散LDL的产生具有遗传背景。然而，它必定受到一些环境因素的影响，因为通过饮食热量限制使血清甘油三酯水平降低时，LDL的异质性会完全恢复到正常的单分散模式。众所周知，LDL在体内和体外都会自发氧化或糖基化。这种修饰后的LDL失去了与经典LDL受体的结合亲和力，并通过清道夫受体被单核细胞衍生的巨噬细胞摄取。由于清道夫受体系统不会下调，它会通过过量摄取LDL促进动脉壁中泡沫细胞的形成，从而积累胆固醇和其他脂质。与大而轻的LDL相比，小而密的LDL被认为更容易氧化或糖基化。因此，它可能会通过这种修饰进一步增加致动脉粥样硬化的潜能。
