Lp(a) is an important contributing factor to the development of atherosclerosis, and in structure is similar to LDL. Given the central role of the LDL receptor (LDL-R) in the metabolism of LDL, we felt that a study of the binding and degradation of Lp(a) facilitated by the LDL-R of human monocyte derived macrophages (HMDM) would be of value in understanding its pathological nature. In this study we compared equimolar amounts of Lp(a) and LDL and found that nearly equal amounts of Lp(a) and LDL bound to the LDL-R of HMDM at 4 degrees C, however the affinity of both lipoproteins was much lower than has been observed for the LDL-R of fibroblasts, being 0.80 muM for Lp(a) and 0.23 muM for LDL. The binding of Lp(a) to HMDM could be competed by 63% with a 50-fold excess of LDL. Degradation of Lp(a) at 37 degree C, unlike 4 degrees C binding, was mainly nonspecific (75% of total Lp(a) degradation) and when compared on an equimolar basis, nearly 6 times more LDL than Lp(a) was processed by the LDL-R pathway in 5 hr. Lower degradation of Lp(a) appears to be the result of lower binding at 37 degree C and a lower degradation rate when compared to LDL. It was not caused by increased intracellular accumulation or retroendocytosis. Degradation of both lipoproteins was only modestly affected by up and down regulation of the LDL-R. Because the binding of LDL at 4 degrees C and degradation at 37 degree C is mainly LDL-R specific, whereas only the 4 degree C binding of Lp(a) is so, suggests that the poor LDL-R dependent degradation of Lp(a) at 37 degree C is caused by a conformational change that is inducted in Lp(a) upon lowering the temperature to 4 degree C which allows better recognition of Lp(a) by the HMDM LDL-R.

译文

Lp(a) 是动脉粥样硬化发展的重要促成因素,并且在结构上与LDL相似。鉴于LDL受体 (ldl-r) 在LDL代谢中的核心作用,我们认为对人类单核细胞衍生的巨噬细胞 (HMDM) 的ldl-r促进Lp(a) 的结合和降解的研究对于了解其病理性质具有价值。在这项研究中,我们比较了等摩尔量的Lp(a) 和LDL,发现几乎相等量的Lp(a) 和LDL在4摄氏度下与HMDM的ldl-r结合,然而,两种脂蛋白的亲和力远低于已观察到的成纤维细胞的ldl-r,0.80 Lp(a) 的muM和LDL的0.23 muM。Lp(a) 与HMDM的结合可通过63% 50倍过量的LDL来竞争。与4 ℃ 结合不同,Lp(a) 在37 ℃ 下的降解主要是非特异性的 (占总Lp(a) 降解的75%),并且当以等摩尔为基础进行比较时,在5小时内通过ldl-r途径处理的LDL比Lp(a) 多近6倍。与LDL相比,Lp(a) 的较低降解似乎是在37 ℃ 下较低结合和较低降解率的结果。它不是由细胞内积累或胞吞作用增加引起的。Ldl-r的上下调节仅对两种脂蛋白的降解产生适度的影响。因为LDL在4 ℃ 的结合和37 ℃ 的降解主要是ldl-r特异性的,而只有4 ℃ 的Lp(a) 的结合是如此,表明Lp(a) 在37摄氏度时的低ldl-r依赖性降解差是由将温度降低到4摄氏度时在Lp(a) 中诱导的构象变化引起的,这允许HMDM ldl-r更好地识别Lp(a)。
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