The Histone Methyltransferase SETDB2 Regulates Abdominal Aortic Aneurysm Formation

The purpose of this project was to establish whether the histone methyltransferase, SETDB2, regulates abdominal aortic aneurysm (AAA) development. We hypothesized that during AAA development, SETDB2 is upregulated, resulting in “turning off” genes are normally protective against pathologic vascular remodeling via methylation H3K9 at gene promoters. Specifically, normal wall existence, a balance exists between matrix metalloproteinases (MMPs), which function break down wall, and tissue inhibitors MMPs (TIMPs), prevent actions on wall. During an imbalance occurs TIMPs, favor MMP activity. Thereby, we Results from Setdb2 TIMP expression, causing proceed unregulated lead destruction C57BL/6 Setdb2f/fLyzCre+ mice, have macrophages deficient underwent angiotensin-II infusion murine model were compared littermate controls with intact expression (C57BL/6 wild type). Aneurysm size measured ultrasound after 28 days infusion. In vivo then isolated analyzed for activity promoter sites TIMPs 1, 2, 3, 4 using chromatin immunoprecipitation. mice had significant reduction formation their wild-type littermates (Fig 1). Furthermore, repression promoters significantly reduced 2). Taken together, these suggest epigenetic macrophages, leading wall.Fig 2H3K9me3 (TIMPs) littermates. collected weeks (n = 6 mice/group).View Large Image Figure ViewerDownload Hi-res image Download (PPT)