Effect of depletion of NR4A3 on vascular calcification [CUTtag_H3K18LA]. Effect of depletion of NR4A3 on vascular calcification [CUTtag_H3K18LA]

Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease (CKD), diabetes mellitus, and aging individuals. We previously showed that orphan nuclear receptor NR4A3 is a key regulator in the progression of apolipoprotein (apo) A-IV-induced atherosclerosis; however, little is known about its role in vascular calcification. NR4A3 expression was upregulated in calcified aortic tissues from CKD mice or 1,25(OH)2VitD3 overload-induced mice, and in human calcified aorta. NR4A3 deficiency preserved VSMCs contractile phenotype, inhibited the expression of osteoblast differentiation-related genes, and reduced calcium deposition in the vasculature. Overall design: Comparative gene expression profiling analysis of RNA-seq data for WT VSMC and NR4A3 VSMC

动脉中层钙化（Medial arterial calcification）是一种与动脉粥样硬化截然不同的慢性全身性血管病变，常见于慢性肾脏病（CKD）患者、糖尿病患者及衰老个体。我们此前的研究表明，孤儿核受体NR4A3是载脂蛋白（apolipoprotein，apo）A-IV诱导的动脉粥样硬化进展的关键调控因子，但目前对其在血管钙化中的作用仍知之甚少。在慢性肾脏病小鼠或1,25(OH)₂VitD3负荷诱导的钙化模型小鼠，以及人钙化主动脉组织中，NR4A3的表达均出现上调。NR4A3基因缺陷可维持血管平滑肌细胞（vascular smooth muscle cells，VSMCs）的收缩表型，抑制成骨细胞分化相关基因的表达，并减少血管内钙沉积。总体实验设计：针对野生型（wild type，WT）血管平滑肌细胞与NR4A3缺陷型血管平滑肌细胞的RNA测序（RNA-seq）数据进行比较基因表达谱分析。