Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery.

Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery.
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DOI:
10.1371/journal.pone.0142904
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Ono K
Ono K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miyamoto S;Usami S;Kuwabara Y;Horie T;Baba O;Hakuno D;Nakashima Y;Nishiga M;Izuhara M;Nakao T;Nishino T;Ide Y;Nakazeki F;Wang J;Ueyama K;Kimura T;Ono K

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最近有报道称,血清中特定的微小RNA(miRNA)水平升高,可作为心血管疾病患者的生物标志物。然而,心包液 (PF) 中的 miRNA 表达谱及其来源尚不清楚。本研究的目的是确定 PF 中 miRNA 的水平与接受心脏手术的患者血清中的 miRNA 水平的关系。对因稳定型心绞痛 (sAP) 和不稳定型 AP (uAP) 接受冠状动脉搭桥术 (CABG) 以及因主动脉瓣狭窄 (AS) 导致主动脉瓣置换术的患者的血清 (S) 和 PF 进行分析,以检测 miRNA。我们分别将这些样本命名为 S-sAP、S-uAP、S-AS、PF-sAP、PF-uAP 和 PF-AS。我们首先测量了 miR-423-5p 的水平,它以前被认为是心力衰竭的生物标志物。 PF 中的 miR-423-5p 水平显着高于血清。尽管 PF-AS、PF-sAP 和 PF-uAP 之间 miR-423-5p 水平没有差异,但与 S-AS 和 S-sAP 相比,S-uAP 中 miR-423-5p 水平显着升高。为了阐明 PF 中 miR-423-5p 的来源,我们测量了同一样本中肌肉富集的 miR-133a 以及血管富集的 miR-126 和 miR-92a 的水平。血清中的 miR-133a 水平显着高于 PF,并且与 S-AS 相比,S-uAP 中的 miR-133a 水平也升高。与PF相比,血清中miR-126水平显着升高,miR-92a水平也有类似趋势。 miR-423-5p 位于 NSRP1 的第一个内含子中。同一区域还有另一种 miRNA,miR-3184,以相反方向编码。体外实验表明,miR-423-5p和miR-3184-3p的双链体比miR-423-5p和miR-133-3p的双链体对RNase具有更强的抵抗力,这可能有助于稳定PF中的miR-423-5p。我们的结果表明 miR-423-5p 在 PF 中富集,血清 miR-423-5p 可能与 uAP 相关。其表达模式与富含肌肉和血管的 miRNA、miR-133a、miR-126 和 miR-92a 不同。
Recently, it has been reported that specific microRNA (miRNA) levels are elevated in serum and can be used as biomarkers in patients with cardiovascular diseases. However, miRNAs expression profiles and their sources in pericardial fluid (PF) are unclear. The purpose of this study was to identify the levels of miRNAs in PF in relation to those in the serum in patients undergoing cardiac surgery. Serum (S) and PF from patients undergoing coronary artery bypass graft (CABG) due to stable angina pectoris (sAP) and unstable AP (uAP) and aortic valve replacement due to aortic stenosis (AS) were analyzed for the detection of miRNAs. We named these samples S-sAP, S-uAP, S-AS, PF-sAP, PF-uAP, and PF-AS, respectively. We first measured the levels of miR-423-5p, which was recognized previously as a biomarker for heart failure. miR-423-5p levels were significantly higher in PF than serum. Although there was no difference in miR-423-5p levels among the PF-AS, PF-sAP, and PF-uAP, its levels were significantly elevated in S-uAP compared with those in S-AS and S-sAP. In order to clarify the source of miR-423-5p in PF, we measured the levels of muscle-enriched miR-133a and vascular-enriched miR-126 and miR-92a in the same samples. miR-133a levels were significantly higher in serum than in PF, and it was elevated in S-uAP compared with S-AS. miR-126 level was significantly increased in serum compared with PF, and the level of miR-92a the similar tendency. miR-423-5p is located in the first intron of NSRP1. There is another miRNA, miR-3184, encoded in the opposite direction in the same region. In vitro experiments indicated that the duplex of miR-423-5p and miR-3184-3p was more resistant to RNase than the duplex of miR-423-5p and miR-133-3p, which may help to stabilize miR-423-5p in the PF. Our results suggested that miR-423-5p is enriched in PF, and serum miR-423-5p may be associate with uAP. Its expression pattern was different to that of muscle- and vascular-enriched miRNAs, miR-133a, miR-126, and miR-92a.