Molecular Genetics, Biochemistry and Microbiology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
Int J Mol Sci. 2022 Aug 31;23(17):9892. doi: 10.3390/ijms23179892.
A preponderance of evidence obtained from genetically modified mice and human population studies reveals the association of apolipoprotein E (apoE) deficiency and polymorphisms with pathogenesis of numerous chronic diseases, including atherosclerosis, obesity/diabetes, and Alzheimer's disease. The human gene is polymorphic with three major alleles, ε2, ε3 and ε4, encoding apoE2, apoE3, and apoE4, respectively. The gene is expressed in many cell types, including hepatocytes, adipocytes, immune cells of the myeloid lineage, vascular smooth muscle cells, and in the brain. ApoE is present in subclasses of plasma lipoproteins, and it mediates the clearance of atherogenic lipoproteins from plasma circulation via its interaction with LDL receptor family proteins and heparan sulfate proteoglycans. Extracellular apoE also interacts with cell surface receptors and confers signaling events for cell regulation, while apoE expressed endogenously in various cell types regulates cell functions via autocrine and paracrine mechanisms. This review article focuses on lipoprotein transport-dependent and -independent mechanisms by which apoE deficiency or polymorphisms contribute to cardiovascular disease, metabolic disease, and neurological disorders.
大量来自基因修饰小鼠和人类群体研究的证据表明，载脂蛋白 E（apoE）缺乏和多态性与许多慢性疾病的发病机制有关，包括动脉粥样硬化、肥胖/糖尿病和阿尔茨海默病。人类基因具有三种主要等位基因 ε2、ε3 和 ε4 的多态性，分别编码 apoE2、apoE3 和 apoE4。该基因在许多细胞类型中表达，包括肝细胞、脂肪细胞、髓系免疫细胞、血管平滑肌细胞和大脑。apoE 存在于血浆脂蛋白的亚类中，通过与 LDL 受体家族蛋白和硫酸乙酰肝素蛋白聚糖的相互作用，介导动脉粥样硬化脂蛋白从血浆循环中的清除。细胞外 apoE 还与细胞表面受体相互作用，为细胞调节赋予信号事件，而各种细胞类型中内源性表达的 apoE 通过自分泌和旁分泌机制调节细胞功能。本文综述了载脂蛋白 E 缺乏或多态性导致心血管疾病、代谢性疾病和神经紊乱的脂蛋白转运依赖和非依赖机制。
