Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
The W. M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Biomed Res Int. 2018 Jun 7;2018:1878964. doi: 10.1155/2018/1878964. eCollection 2018.
A murine genetic model of LDL-cholesterol- (LDL-C-) driven atherosclerosis, based on complete deficiencies of both the LDL-receptor () and key catalytic component of an apolipoprotein B-edisome complex (), which converts apoB-100 to apoB-48, has been extensively characterized. These gene deficiencies allow high levels of apoB-100 to be present and inefficiently cleared, thus leading to very high levels of LDL-C in mice on a normal diet. Many key features of atherosclerotic plaques observed in human familial hypercholesterolemia are found in these mice as they are allowed to age through 72 weeks. The general characteristics include the presence of high levels of LDL-C in plasma and macrophage-related fatty streak formation in the aortic tree, which progressively worsens with age. More specifically, plaque found in the aortic sinuses contains a lipid core with relatively high numbers of macrophages and a smooth muscle cell -actin- and collagen-containing cap, which thins with age. These critical features of plaque progression suggest that the / mouse line presents a superior model of LDL-C-driven atherosclerosis.
一种基于 LDL 受体（）和载脂蛋白 B 分泌小体复合物关键催化成分（）完全缺失的 LDL-胆固醇（LDL-C）驱动的动脉粥样硬化的小鼠遗传模型，已被广泛研究。这些基因缺陷使大量的 apoB-100 存在且清除效率低下，从而导致在正常饮食下的小鼠中 LDL-C 水平非常高。在这些小鼠中，随着年龄的增长到 72 周时，可观察到人类家族性高胆固醇血症中观察到的许多动脉粥样硬化斑块的关键特征。一般特征包括血浆中 LDL-C 水平高和主动脉树中与巨噬细胞相关的脂肪条纹形成，随着年龄的增长而逐渐恶化。更具体地说，在主动脉窦中发现的斑块含有富含巨噬细胞的脂质核心和富含平滑肌细胞 -actin-和胶原蛋白的帽，随着年龄的增长而变薄。这些斑块进展的关键特征表明，/ 小鼠系提供了一种优越的 LDL-C 驱动的动脉粥样硬化模型。
