The Long Noncoding RNA RP11-728F11.4 Promotes Atherosclerosis

Objective: Noncoding RNAs are emerging as important players in gene regulation and cardiovascular diseases. Their roles the pathogenesis of atherosclerosis not fully understood. The purpose this study was to determine role played by a previously uncharacterized long noncoding RNA, RP11-728F11.4, development mechanisms which it acts. Approach Results: Expression microarray analysis revealed that atherosclerotic plaques had increased expression RP11-728F11.4 well cognate FXYD6 (FXYD domain containing ion transport regulator 6), encodes modulator Na + /K -ATPase. In vitro experiments showed interacted with RNA-binding protein EWSR1 (Ewings sarcoma RNA binding protein-1) upregulated expression. Lentivirus-induced overexpression cultured monocytes-derived macrophages resulted higher -ATPase activity, intracellular cholesterol accumulation, proinflammatory cytokine production. effects were enhanced siRNA-mediated knockdown reduced downregulation FXYD 6. vivo apoE knockout mice fed Western diet demonstrated production augmented lesions. Conclusions: promotes atherosclerosis, an influence on homeostasis molecule production, thus representing potential therapeutic target. Graphic Abstract: A graphic abstract is available for article.