The effect of A-196 and TMP-269 epigenetic enzyme inhibitor treatments on endothelial cells and fibroblasts

Epigenetic-based therapy has gained interest with regard to cardiovascular diseases. However, cell-type-specific effects and the limited complexity of cellular interactions in the screening methods causes challenges in finding novel drug candidates. Using a library of epigenetic modulator compounds, we found that A-196 and TMP-269 demonstrated functional effects in a fibrin bead angiogenesis assay. To study how these epigenetic enzyme inhibitors affect genome-wide gene expression profiles, we performed RNA-Seq of human umbilical vein endothelial cells (HUVEC) and human pulmonary fibroblasts (HPF) treated with these compounds. Overall design: Cells were subjected to 72 h chemical treatment, followed by RNA-Seq using an mRNA 3' tag approach aimed at gene expression quantification.

基于表观遗传学的疗法在心血管疾病领域已受到广泛关注。然而，筛选方法中存在的细胞类型特异性效应以及细胞互作复杂度受限的问题，为新型候选药物的研发带来了挑战。本研究借助表观遗传调控化合物文库开展实验，发现A-196与TMP-269在纤维蛋白微球血管生成试验中展现出功能调控效应。为探究这些表观遗传酶抑制剂如何影响全基因组基因表达谱，我们对经上述化合物处理的人脐静脉内皮细胞（HUVEC）以及人肺成纤维细胞（HPF）开展了RNA-Seq实验。实验整体设计：将细胞施以72小时的化合物处理，随后采用靶向基因表达定量的mRNA 3'端标签测序法开展RNA-Seq实验。