Of the glomerular disorders that occur due to apolipoprotein E (apoE) mutations, apoE2 homozygote glomerulopathy and lipoprotein glomerulopathy (LPG) have been characterized. ApoE2 homozygote glomerulopathy has been found in individuals expressing homozygous apoE2/2. This was characterized histologically by glomerulosclerosis with marked infiltration of foam cells derived from macrophages, and occasionally with non-lamellated lipoprotein thrombi. Recently, several cases of apoE Toyonaka (Ser197Cys) combined with homozygous apoE2/2 have been reported, in which non-immune membranous nephropathy-like features were observed in glomeruli. Interestingly, in these cases, apoE accumulation was identified by tandem mass spectrometry. Therefore, it is speculated that these findings may arise from apoE molecules without lipids, which result from hinge damage by apoE Toyonaka and may cross the glomerular basement membrane as small molecules. LPG is primarily associated with heterozygous apoE mutations surrounding the low-density lipoprotein-receptor binding site, and it is histologically characterized by lamellated lipoprotein thrombi that lack foam cells. Recent studies have suggested that LPG can be induced by thermodynamic destabilization, hydrophobic surface exposure, and the aggregation of apoE resulting from the incompatibility of apoE mutated residues within helical regions. Additionally, apoE5 may play a supporting role in the development of LPG and in lipid-induced kidney diseases via hyperlipoproteinemia. Thus, it is interesting that many apoE mutations contribute to characteristic glomerular disorders through various mechanisms. In particular, macrophages may uptake lipoproteins into the cytoplasm and contribute to the development of apoE2 homozygote glomerulopathy as foam cells, and their dysfunction may contribute to the accumulation of lipoproteins in the glomerulus, causing lipoprotein thrombi in LPG.

中文翻译：

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载脂蛋白E相关的肾小球疾病。

在由于载脂蛋白E（apoE）突变而发生的肾小球疾病中，已经鉴定出apoE2纯合子肾小球病和脂蛋白肾小球病（LPG）。已经在表达纯合的apoE2 / 2的个体中发现了ApoE2纯合子肾小球病。组织学上的特点是肾小球硬化，巨噬细胞源性泡沫细胞明显浸润，偶有非分层脂蛋白血栓。最近，已经报道了几例apoE丰中（Ser197Cys）与纯合apoE2 / 2结合的病例，其中在肾小球中观察到了非免疫性膜性肾病样特征。有趣的是，在这些情况下，通过串联质谱鉴定了apoE的积累。因此，推测这些发现可能是由于无脂质的apoE分子引起的，这是由apoE Toyonaka造成的铰链损坏造成的，并可能以小分子的形式穿过肾小球基底膜。LPG主要与低密度脂蛋白受体结合位点周围的杂合性apoE突变有关，其组织学特征是缺乏泡沫细胞的层状脂蛋白血栓形成。最近的研究表明，LPG可以由热力学不稳定，疏水表面暴露和螺旋区域内apoE突变残基的不相容性引起的apoE聚集诱导。此外，apoE5可能在LPG的发展以及通过高脂蛋白血症的脂质诱导的肾脏疾病中起辅助作用。因此，有趣的是，许多apoE突变通过各种机制导致了特征性肾小球疾病。特别是，