The LipoGlo reporter system for sensitive and specific monitoring of atherogenic lipoproteins
Year: 2019
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: U.S. Department of Health and Human Services, Carnegie Institution of Washington, Carnegie Institution for Science, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1011396508, G3868085875, Acquisition of GE Typhoon FLA9500 Variable Mode Imager, In vivo HTS assay for novel modulators, Discovery and characterization of novel regulators of Apo-B in larval zebrafish, G6380816169, Cellular and Molecular Biology, G8000303052, G8235518024, Systematic Vertebrate Functional Genomics, Mayo Center for Cell Signaling in Gastroenterology, Cellular and Molecular Biology, Identifying genes required for digestive physiology and lipid metabolism
OpenAlex ID: W2965510852
