用于敏感和特异性监测动脉粥样脂蛋白的 LipoGlo 报告系统。

The LipoGlo reporter system for sensitive and specific monitoring of atherogenic lipoproteins.

机构信息

Carnegie Institution for Science Department of Embryology, 3520 San Martin Drive, Baltimore, MD, 21218, USA.

Johns Hopkins University Department of Biology, 3400N Charles Street, Baltimore, MD, 21218, USA.

出版信息

Nat Commun. 2019 Jul 31;10(1):3426. doi: 10.1038/s41467-019-11259-w.

Apolipoprotein-B (ApoB) is the structural component of atherogenic lipoproteins, lipid-rich particles that drive atherosclerosis by accumulating in the vascular wall. As atherosclerotic cardiovascular disease is the leading cause of death worldwide, there is an urgent need to develop new strategies to prevent lipoproteins from causing vascular damage. Here we report the LipoGlo system, which uses a luciferase enzyme (NanoLuc) fused to ApoB to monitor several key determinants of lipoprotein atherogenicity including particle abundance, size, and localization. Using LipoGlo, we comprehensively characterize the lipoprotein profile of individual larval zebrafish and collect images of atherogenic lipoprotein localization in an intact organism. We report multiple extravascular lipoprotein localization patterns, as well as identify Pla2g12b as a potent regulator of lipoprotein size. ApoB-fusion proteins thus represent a sensitive and specific approach to study atherogenic lipoproteins and their genetic and small molecule modifiers.

载脂蛋白 B（ApoB）是致动脉粥样硬化脂蛋白的结构成分，富含脂质的颗粒通过在血管壁中积累而导致动脉粥样硬化。由于动脉粥样硬化性心血管疾病是全球死亡的主要原因，因此迫切需要开发新的策略来防止脂蛋白引起血管损伤。在这里，我们报告了 LipoGlo 系统，该系统使用与 ApoB 融合的荧光素酶（NanoLuc）来监测脂蛋白致动脉粥样硬化性的几个关键决定因素，包括颗粒丰度、大小和定位。使用 LipoGlo，我们全面描述了个体斑马鱼幼虫的脂蛋白谱，并在完整的生物体中收集致动脉粥样硬化脂蛋白定位的图像。我们报告了多种血管外脂蛋白定位模式，并确定 Pla2g12b 是脂蛋白大小的有效调节剂。因此，ApoB 融合蛋白是研究致动脉粥样硬化脂蛋白及其遗传和小分子修饰剂的敏感和特异的方法。