Profiling of Histone Modifications Reveals Epigenomic Dynamics During Abdominal Aortic Aneurysm Formation in Mouse Models.

Frontiers in Cardiovascular Medicine
Jacob GreenwayNeal L Weintraub

Abstract

Introduction: Abdominal aortic aneurysms (AAA) are characterized by localized inflammation, extracellular matrix degradation, and apoptosis of smooth muscle cells, which together lead to progressive and irreversible aortic dilation. Major risk factors for AAA include smoking and aging, both of which prominently alter gene expression via epigenetic mechanisms, including histone methylation (me) and acetylation (ac).However, little is known about epigenomic dynamics during AAA formation. Here, we profiled histone modification patterns in aortic tissues during AAA formation in two distinct mouse models; (1) angiotensin II (AngII) infusion in low density lipoprotein receptor (LDLR) knockout (KO) mice, and (2) calcium chloride (CaCl2) application in wild type mice. Methods and Results: AAA formed in both models, in conjunction with enhanced macrophage infiltration, elastin degradation and matrix metalloproteinases expression as evaluated by immunohistochemistry. To investigate the histone modification patterns during AAA formation, total histone proteins were extracted from AAA tissues, and histone H3 modifications were quantified using profiling kits. Intriguingly, we observed dynamic changes in histone H3 modifications of lysine (...Continue Reading

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Methods Mentioned

BETA
Assay
immunoprecipitation
acetylation
ChIP-Seq
histone acetylation
dissections

Software Mentioned

R package ChIPseeker
Graphpad

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