ABSTRACT

Cardiovascular disease (CVD) has been identified as the leading cause of premature deaths in rheumatoid arthritis (RA), accounting for about 40 to 50% of all deaths. Macrophage inflammation is regarded as a key point to link to the two diseases. Recently, long non-coding RNAs (lncRNAs) have acknowledged as a regulator of inflammation significantly. Here, we firstly found that lncRNA myocardial infarction associated transcript (lncRNA MIAT), a crucial lncRNA to regulate CVD, expressed increasingly in synovium and myocardial tissues of collagen-induced arthritis (CIA) mice. Besides, we also verified that the increased infiltration of macrophage occurred in those tissues of the CIA. In vitro, we found that macrophage inflammation induced by LPS could up-regulate lncRNA MIAT expression. LncRNA MIAT seemed to inhibit the expression of IL-1β, TNF-ɑ and be suppressed by ATP-induced NLRP3 inflammasome activation pathway. Therefore, these data indicated an anti-inflammatory effect of lncRNA MIAT in macrophage and an original research direction for high cardiovascular risk in RA.

摘要

心血管疾病 (CVD) 已被确定为类风湿关节炎 (RA) 过早死亡的主要原因，约占所有死亡人数的 40% 至 50%。巨噬细胞炎症被认为是连接这两种疾病的关键点。最近，长链非编码 RNA (lncRNA) 已被公认为是炎症的重要调节因子。在这里，我们首先发现 lncRNA 心肌梗死相关转录物 (lncRNA MIAT) 是调节 CVD 的关键 lncRNA，它在胶原诱导的关节炎 (CIA) 小鼠的滑膜和心肌组织中越来越多地表达。此外，我们还证实在 CIA 的这些组织中发生了巨噬细胞浸润的增加。在体外，我们发现 LPS 诱导的巨噬细胞炎症可以上调 lncRNA MIAT 表达。LncRNA MIAT 似乎抑制 IL-1β 的表达，TNF-ɑ 并被 ATP 诱导的 NLRP3 炎性体激活途径抑制。因此，这些数据表明 lncRNA MIAT 在巨噬细胞中的抗炎作用和 RA 高心血管风险的原始研究方向。