A therosclerosis is the underlying cause of cardiovascular disease (CVD), which is the leading cause of mortality worldwide.1 CVD is initiated by the accumulation of lipids, necrotic cells, and fibrous elements in the neointima of medium and large arteries. 2,3 The primary cells that contribute to atherosclerotic lesion formation are endothelial cells, vascular smooth muscle cells, and macrophages. [4][5][6] Plaque formation results from the infiltration of circulating monocytes in the subendothelial space, where they differentiate into macrophages and subsequently internalize modified lipoproteins and further differentiate into foam cells. 7 Therefore, further clarification of the mechanisms leading to macrophage accumulation is important to prevent plaque rupture and subsequent life-threatening clinical complications, such as myocardial infarction and stroke. See accompanying editorial on page 7The nuclear receptor superfamily is composed of transcription factors that positively and negatively regulate gene expression, which not only influence lipid metabolism at the systemic level but also regulate lipid homeostasis and inflammation in macrophages, endothelial cells, and smooth muscle cells within the arterial walls. 8,9 The nuclear factor I (NFI) family of site-specific DNA-binding proteins are critical regulators of gliogenesis in the developing central nervous system.10,11 NFIA, a member of the NFI family, can modulate DNA replication and transcription through binding to duplex DNA containing the TTGGC motif or 5′-TTGGCN 5 GCCAA-3′ consensus sequence. 12 Many studies have shown that NFIA plays critical roles in specifying glial cell identity and promoting astrocyte differentiation during embryonic development. 10,11 In addition, a recent study demonstrated that NFIA was functionally required for proper adipocyte differentiation and lipid droplet formation. Overexpression of NFIA in 3T3-L1 cells could significantly result in lipid droplet formation without differentiation stimulus. Overexpression of dominantnegative NFIA or small interfering RNA (siRNA)-mediated knockdown of NFIA could markedly inhibit lipid accumulation during differentiation 13 . However, no publication has © 2014 American Heart Association, Inc. Objective-Cardiovascular disease caused by atherosclerosis is the number one cause of death in Western countries and threatens to become the major cause of morbidity and mortality worldwide. Long noncoding RNAs are emerging as new players in gene regulation, but how long noncoding RNAs operate in the development of atherosclerosis remains unclear. Approach and Results-Using microarray analysis, we found that long noncoding RNA RP5-833A20.1 expression was upregulated, whereas nuclear factor IA (NFIA) expression was downregulated in human acute monocytic leukemia macrophage-derived foam cells. Moreover, we showed that long noncoding RNA RP5-833A20.1 may decreases NFIA expression by inducing hsa-miR-382-5p expression in vitro. We found that the RP5-833A20.1/hsa-miR-382-5p/NFIA pathway is essenti...

No abstract

AimsATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins, which then form nascent HDL, a key step in the mechanism of reverse cholesterol transport (RCT). While a series of microRNAs (miRNAs) have been identified as potent post-transcriptional regulators of lipid metabolism, their effects on ABCA1 function and associated mechanisms remain unclear.Methods and ResultsABCA1 was identified as a potential target of miR-144-3p, based on the results of bioinformatic analysis and the luciferase reporter assay, and downregulated after transfection of cells with miR-144-3p mimics, as observed with real-time PCR and western blot. Moreover, miR-144-3p mimics (agomir) enhanced the expression of inflammatory factors, including IL-1β, IL-6 and TNF-α, in vivo and in vitro, inhibited cholesterol efflux in THP-1 macrophage-derived foam cells, decreased HDL-C circulation and impaired RCT in vivo, resulting in accelerated pathological progression of atherosclerosis in apoE−/− mice. Clinical studies additionally revealed a positive correlation of circulating miR-144-3p with serum CK, CK-MB, LDH and AST in subjects with AMI.ConclusionsOur findings clearly indicate that miR-144-3p is essential for the regulation of cholesterol homeostasis and inflammatory reactions, supporting its utility as a potential therapeutic target of atherosclerosis and a promising diagnostic biomarker of AMI.