Absence of Interferon Regulatory Factor 1 Protects Against Atherosclerosis in Apolipoprotein E-Deficient Mice

Theranostics
Meng DuKai Huang

Abstract

Deciphering the molecular and cellular processes involved in foam cell formation is critical to understanding the pathogenesis of atherosclerosis. Interferon regulatory factor 1 (IRF1) was first identified as a transcriptional regulator of type-I interferons (IFNs) and IFN inducible genes. Our study aims to explore the role of IRF1 in atherosclerotic foam cell formation and understand the functional diversity of IRF1 in various cell types contributing to atherosclerosis. Methods: We induced experimental atherosclerosis in ApoE-/-IRF1-/- mice and evaluated the effect of IRF1 on disease progression and foam cell formation. Results: IRF1 expression was increased in human and mouse atherosclerotic lesions. IRF1 deficiency inhibited modified lipoprotein uptake and promoted cholesterol efflux, along with altered expression of genes implicated in lipid metabolism. Gene expression analysis identified scavenger receptor (SR)-AI as a regulated target of IRF1, and SR-AI silencing completely abrogated the increased uptake of modified lipoprotein induced by IRF1. Our data also explain a mechanism underlying endotoxemia-complicated atherogenesis as follows: two likely pro-inflammatory agents, oxidized low-density lipoprotein (ox-LDL) and bac...Continue Reading

Citations

Mar 15, 2020·BMC Cardiovascular Disorders·Xilan YangChen Qu
Apr 4, 2021·Molecular and Cellular Biochemistry·Ampadu O JacksonShiyin Long
Aug 9, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Atif ZafarGanapati H Mahabeleshwar
Sep 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Meng DuKai Huang

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Methods Mentioned

BETA
coronary artery bypass
PCR
Assay
immunoprecipitation
Biosample
flow cytometry
ChIP
nuclear translocation
immunoprecipitation assay
pull-down

Software Mentioned

GraphPad Prism
Image J

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