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

Nature Communications
James H ThiererSteven Farber

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 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.

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Citations

Nov 25, 2020·Autophagy·Devesh C Pant, Taras Y Nazarko
Feb 5, 2021·Journal of Lipid and Atherosclerosis·Jun Ka, Suk-Won Jin
Mar 16, 2021·Frontiers in Cell and Developmental Biology·Dandan TangRuilin Zhang
Apr 9, 2021·Developmental Biology·Misty R Riddle, Chi-Kuo Hu
May 11, 2020·Current Biology : CB·Benjamin R TroutwineRyan S Gray

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Methods Mentioned

BETA
electrophoresis
genotyping
electron microscopy
transgenic
dissection
PCR

Software Mentioned

LipoGlo
R
FusX assembly system
Mojo Hand
ImageJ
XLSTAT
WRS2

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