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标题：The role of long noncoding RNA Nron in atherosclerosis development and plaque stability
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作者：Meng Du ; Cheng Wang ; Liuye Yang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：3
页码：1-23
DOI：10.1016/j.isci.2022.103978
语种：English
出版社：Elsevier
摘要：SummaryThe major clinical consequences of atherosclerosis such as myocardial infarction or stroke are because of thrombotic events associated with acute rupture or erosion of an unstable plaque. Here, we identify an lncRNA Noncoding Repressor of NFAT (Nron) as a critical regulator of atherosclerotic plaque stability. Nron overexpression (OE) in vascular smooth muscle cells (VSMC) induces a highly characteristic architecture of more-vulnerable plaques, while Nron knockdown (KD) suppresses the development of atherosclerosis and favors plaque stability. Mechanistically, Nron specifically binds to and negatively regulates NFATc3, thus inhibiting the proliferation and promoting the apoptosis of VSMCs. Moreover, we also provide evidence that Nron increases the production and secretion of VEGFA from VSMCs, which functions as a paracrine factor to enhance intra-plaque angiogenesis. All of these effects contribute to plaque instability. Genetic or pharmacological inhibition of Nron may have potential for future therapy of atherosclerosis.Graphical abstractDisplay OmittedHighlights•Nron promotes atherosclerosis progression and contributes to plaque instability•Nron negatively regulates NFATc3 activity and impairs VSMC function•Nron increases VEGFA production and promotes intra-plaque angiogenesisPathophysiology; Molecular biology; Functional aspects of cell biology