PLGA-PEG-PLGA Thermogel from PolySciTech used in study to understand neointimal hyperplasia

 

Neointimal hyperplasia is a process by which injured vessels will initiate in-growth of tissue. This process is particularly problematic during stenosis as the growing tissue blocks the interior of the stent and recloses the vessel. Recently, researchers from University of Virginia and Ohio State University used PLGA-PEG-PLGA (Cat# AK012) from PolySciTech (www.polyscitech.com) to delivery EZH1/2 inhibitor (UNC1999) as a way to model healing with this pathway blocked off. This understanding of vessel healing process can assist with designing more effective means of stenosis. Read more: Zhang, Mengxue, Go Urabe, Hatice Gulcin Ozer, Xiujie Xie, Amy Webb, Takuro Shirasu, Jing Li et al. "Angioplasty induces epigenomic remodeling in injured arteries." Life Science Alliance 5, no. 5 (2022). https://www.life-science-alliance.org/content/5/5/e202101114.abstract

“Abstract: Neointimal hyperplasia/proliferation (IH) is the primary etiology of vascular stenosis. Epigenomic studies concerning IH have been largely confined to in vitro models, and IH-underlying epigenetic mechanisms remain poorly understood. This study integrates information from in vivo epigenomic mapping, conditional knockout, gene transfer and pharmacology in rodent models of IH. The data from injured (IH-prone) rat arteries revealed a surge of genome-wide occupancy by histone-3 lysine-27 trimethylation (H3K27me3), a gene-repression mark. This was unexpected in the traditional view of prevailing post-injury gene activation rather than repression. Further analysis illustrated a shift of H3K27me3 enrichment to anti-proliferative genes, from pro-proliferative genes where gene-activation mark H3K27ac(acetylation) accumulated instead. H3K27ac and its reader BRD4 (bromodomain protein) co-enriched at Ezh2; conditional BRD4 knockout in injured mouse arteries reduced H3K27me3 and its writer EZH2, which positively regulated another pro-IH chromatin modulator UHRF1. Thus, results uncover injury-induced loci-specific H3K27me3 redistribution in the epigenomic landscape entailing BRD4→EZH2→UHRF1 hierarchical regulations. Given that these players are pharmaceutical targets, further research may help improve treatments of IH.”