Molecular Biology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico D.F.
Metabolism. 2013 Apr;62(4):492-8. doi: 10.1016/j.metabol.2012.09.010. Epub 2012 Oct 22.
The kidney has been proposed to play a central role in apo AI catabolism, suggesting that HDL structure is determined, at least in part, by this organ. Here, we aimed at determining the effects of a renal mass reduction on HDL size distribution, lipid content, and apo AI turnover.
We characterized HDL subclasses in rabbits with a 75% reduction of functional renal mass (Nptx group), using enzymatic staining of samples separated on polyacrylamide electrophoresis gels, and also performed kinetic studies using radiolabeled HDL-apo AI in this animal model.
Creatinine clearance was reduced to 35% after nephrectomy as compared to the basal values, but without increased proteinuria. A slight, but significant modification of the relative HDL size distribution was observed after nephrectomy, whereas cholesterol plasma concentrations gradually augmented from large HDL2b (+54%) to small HDL3b particles (+150%, P<0.05). Cholesteryl esters were the increased fraction; in contrast, free cholesterol phospholipids and triglycerides of HDL subclasses were not affected by nephrectomy. HDL-apo AI fractional catabolic rates were similar to controls.
Reduction of functional renal mass is associated to enrichment of HDL subclasses with cholesteryl esters. Structural abnormalities were not related to a low apo AI turnover, suggesting renal contribution to HDL remodeling beyond being just a catabolic site for these lipoproteins.
肾脏被认为在载脂蛋白 AI(apo AI)的代谢中起核心作用,这表明 HDL 的结构至少部分由该器官决定。在此,我们旨在确定肾部分切除对 HDL 颗粒大小分布、脂质含量和 apo AI 周转率的影响。
我们使用酶促染色法对接受 75%肾部分切除的兔子(Nptx 组)进行了 HDL 亚类的特征分析,这种方法可对聚丙烯酰胺电泳凝胶分离的样本进行分析,还使用放射性标记的 HDL-apo AI 在该动物模型中进行了动力学研究。
与基础值相比,手术后肌酐清除率降低至 35%,但蛋白尿没有增加。肾切除后,相对 HDL 大小分布略有但显著改变,而胆固醇血浆浓度逐渐从大 HDL2b(增加 54%)增加到小 HDL3b 颗粒(增加 150%,P<0.05)。胆固醇酯是增加的部分;相比之下,HDL 亚类的游离胆固醇、磷脂和甘油三酯不受肾切除的影响。HDL-apo AI 的分解代谢率与对照组相似。
功能性肾质量的减少与富含胆固醇酯的 HDL 亚类有关。结构异常与 apo AI 周转率低无关,这表明肾脏对 HDL 重塑的贡献不仅是这些脂蛋白的代谢部位。