OBJECTIVE Long noncoding RNAs (lncRNAs) are an emergent class of molecules with diverse functional roles, widely expressed in human physiology and disease. Although some lncRNAs have been identified in cardiovascular disease, their potential as novel targets in the prevention of atherosclerosis is unknown. We set out to discover important lncRNAs in unstable plaque and gain insight into their functional relevance. Approach and Results: Analysis of RNA sequencing previously performed on stable and unstable atherosclerotic plaque identified a panel of 47 differentially regulated lncRNAs. We focused on LINC01272, a lncRNA upregulated in unstable plaque previously detected in inflammatory bowel disease, which we termed PELATON (plaque enriched lncRNA in atherosclerotic and inflammatory bowel macrophage regulation). Here, we demonstrate that PELATON is highly monocyte- and macrophage-specific across vascular cell types, and almost entirely nuclear by cellular fractionation (90%-98%). In situ hybridization confirmed enrichment of PELATON in areas of plaque inflammation, colocalizing with macrophages around the shoulders and necrotic core of human plaque sections. Consistent with its nuclear localization, and despite containing a predicted open reading frame, PELATON did not demonstrate any protein-coding potential in vitro. Functionally, knockdown of PELATON significantly reduced phagocytosis, lipid uptake and reactive oxygen species production in high-content analysis, with a significant reduction in phagocytosis independently validated. Furthermore, CD36, a key mediator of phagocytic oxLDL (oxidized low-density lipoprotein) uptake was significantly reduced with PELATON knockdown. CONCLUSIONS PELATON is a nuclear expressed, monocyte- and macrophage-specific lncRNA, upregulated in unstable atherosclerotic plaque. Knockdown of PELATON affects cellular functions associated with plaque progression.

中文翻译：

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在动脉粥样硬化巨噬细胞调节 (PELATON) 中的新型斑块富集长非编码 RNA。

目的 长链非编码 RNA (lncRNA) 是一类新兴的分子，具有多种功能作用，在人类生理和疾病中广泛表达。尽管已经在心血管疾病中发现了一些 lncRNA，但它们作为预防动脉粥样硬化的新靶点的潜力尚不清楚。我们着手在不稳定斑块中发现重要的 lncRNA，并深入了解它们的功能相关性。方法和结果：之前对稳定和不稳定动脉粥样硬化斑块进行的 RNA 测序分析确定了一组 47 个差异调节的 lncRNA。我们专注于 LINC01272，这是一种在先前在炎症性肠病中检测到的不稳定斑块中上调的 lncRNA，我们将其称为 PELATON（斑块富集的 lncRNA 在动脉粥样硬化和炎症性肠巨噬细胞调节中）。这里，我们证明了 PELATON 在各种血管细胞类型中具有高度的单核细胞和巨噬细胞特异性，并且几乎完全通过细胞分级分离 (90%-98%)。原位杂交证实了 PELATON 在斑块炎症区域的富集，与肩部周围的巨噬细胞和人类斑块切片的坏死核心共定位。与其核定位一致，并且尽管包含预测的开放阅读框，但 PELATON 在体外没有表现出任何蛋白质编码潜力。在功能上，PELATON 的敲低在高内涵分析中显着降低了吞噬作用、脂质摄取和活性氧物质的产生，并独立验证了吞噬作用显着降低。此外，CD36、PELATON 敲低后，吞噬性 oxLDL（氧化低密度脂蛋白）摄取的关键介质显着降低。结论 PELATON 是一种核表达的单核细胞和巨噬细胞特异性 lncRNA，在不稳定的动脉粥样硬化斑块中上调。PELATON 的敲除会影响与斑块进展相关的细胞功能。