Koyama Satoshi, Kuragaichi Takashi, Sato Yukihito, Kuwabara Yasuhide, Usami Shunsuke, Horie Takahiro, Baba Osamu, Hakuno Daihiko, Nakashima Yasuhiro, Nishino Tomohiro, Nishiga Masataka, Nakao Tetsushi, Arai Hidenori, Kimura Takeshi, Ono Koh
Department of Cardiovascular Medicine, Graduate School of MedicineKyoto University54 Shogoinkawahara-cho, Sakyo-kuKyoto606-8507Japan.
Department of Cardiovascular MedicineHyogo Prefectural Amagasaki General Medical Center2-17-77 Higashinaniwa-choAmagasakiHyogo660-8550Japan.
ESC Heart Fail. 2017 May;4(2):112-121. doi: 10.1002/ehf2.12123. Epub 2016 Dec 1.
Recent studies have shown that serum microRNA (miR) abundance is informative for the diagnosis or prognosis of heart failure. However, the dynamics and kinetics of miRs in acute heart failure are largely unknown. Serial measurement and analysis of serum miRs changes in individuals along their therapeutic course could reduce inter-individual variation and should detect potentially important serum miRs related to disease mechanisms. Based on this concept, we profiled serum miR signatures of blood samples that were obtained sequentially on the day of admission and on hospital Day 7.
This prospective, observational study included 42 consecutive acute heart failure patients (74 ± 1 years old, 24 male). From admission to Day 7, most of the patients showed clinical improvement. In such a cohort, we detected several fluctuations of serum miRs by two distinct screening methods (quantitative PCR and high-throughput sequencing). One of these fluctuating serum miRs, miR-122-5p, decreased significantly from Day 1 to Day 7 [median arbitrary unit (1st:3rd quantile value); 4.62 [2.39:12.3] to 3.07 [1.67:5.39], = 0.007]. This fluctuation was significantly correlated with changes in serum liver function markers (estimated coefficient and 95% confidence interval; vs change in aspartate aminotransferase 1.69, 0.890-2.484, < 0.001 and = 0.560, vs change in alanine aminotransferase 1.09, 0.406-1.771, = 0.007 and = 0.428).
The serum miR signature of patients with acute heart failure might indicate the severity of the disease or patients' response to therapeutic intervention. Notably, serum miR-122-5p levels reflect liver damage in this condition.
近期研究表明,血清微小RNA(miR)丰度对心力衰竭的诊断或预后具有参考价值。然而,急性心力衰竭中miR的动态变化和动力学在很大程度上尚不清楚。对个体治疗过程中血清miR变化进行连续测量和分析,可减少个体间差异,并应能检测出与疾病机制相关的潜在重要血清miR。基于这一概念,我们分析了在入院当天和住院第7天连续采集的血样的血清miR特征。
这项前瞻性观察性研究纳入了42例连续的急性心力衰竭患者(74±1岁,24例男性)。从入院到第7天,大多数患者临床症状改善。在这样一个队列中,我们通过两种不同的筛选方法(定量PCR和高通量测序)检测到血清miR的几次波动。其中一种波动的血清miR,即miR-122-5p,从第1天到第7天显著下降[中位数任意单位(第1四分位数:第3四分位数);4.62[2.39:12.3]至3.07[1.67:5.39],P = 0.007]。这种波动与血清肝功能标志物的变化显著相关(估计系数和95%置信区间;与天冬氨酸转氨酶变化相比为1.69,0.890 - 2.484,P < 0.001且R = 0.560,与丙氨酸转氨酶变化相比为1.09,0.406 - 1.771,P = 0.007且R = 0.428)。
急性心力衰竭患者的血清miR特征可能表明疾病的严重程度或患者对治疗干预的反应。值得注意的是,在这种情况下,血清miR-122-5p水平反映肝脏损伤。