LipoGlo: A sensitive and specific reporter of atherogenic lipoproteins

Abstract

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 are able to comprehensively characterize the lipoprotein profile of individual larval zebrafish and collect the first images of atherogenic lipoprotein localization in an intact organism. We discover multiple unexpected extravascular lipoprotein localization patterns, as well as identify pla2g12b as a potent regulator of lipoprotein size. ApoB-fusion proteins thus represent a uniquely sensitive and specific approach to study atherogenic lipoproteins and their genetic and small molecule modifiers.