Kakimoto Yu, Tanaka Masayuki, Hayashi Hideki, Yokoyama Keiko, Osawa Motoki
Department of Forensic Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Support Center for Medical Research and Education, Tokai University, Kanagawa, Japan.
Heliyon. 2018 Jun 4;4(6):e00639. doi: 10.1016/j.heliyon.2018.e00639. eCollection 2018 Jun.
Cardiac hypertrophy is a well-known risk factor for heart failure and sudden cardiac death (SCD). On the other hand, physiological cardiac hypertrophy is often observed in young healthy men, and it is difficult to predict SCD in cardiac hypertrophy subjects who do not show symptoms of heart failure. MicroRNAs (miRNAs) widely regulate biological activity and play pivotal roles in heart failure progression. In this study, we investigated whether miRNA expression is altered in SCD with cardiac hypertrophy (SCH).
Cardiac tissues were sampled at autopsy from SCH patients, compensated cardiac hypertrophy (CCH) subjects who died of causes other than heart failure, and control cases without cardiac hypertrophy or heart failure. After histopathological examination, we performed deep sequencing and quantitative PCR of cardiac miRNAs.
Although SCH and CCH showed indistinguishable histological features, their miRNA expression signatures were distinct. Among the 240 miRNAs stably detected in the heart, 8 were differentially expressed between SCH and CCH. Specifically, miR-221 increased in SCH compared to CCH and control cases. The significant elevation of cardiac miR-221 in SCH patients is correlated with lethal outcomes. Thus, our results indicate that an elevated miR-221 level is potentially associated with an increased risk of SCD in subjects with cardiac hypertrophy.
心脏肥大是心力衰竭和心源性猝死(SCD)的一个众所周知的危险因素。另一方面,生理性心脏肥大在年轻健康男性中经常可见,并且很难预测在没有心力衰竭症状的心脏肥大患者中发生心源性猝死的风险。微小RNA(miRNA)广泛调节生物活性,并在心力衰竭进展中起关键作用。在本研究中,我们调查了在伴有心脏肥大的心源性猝死(SCH)中miRNA表达是否发生改变。
从SCH患者、因心力衰竭以外原因死亡的代偿性心脏肥大(CCH)受试者以及无心脏肥大或心力衰竭的对照病例的尸检中采集心脏组织。经过组织病理学检查后,我们对心脏miRNA进行了深度测序和定量PCR。
尽管SCH和CCH显示出难以区分的组织学特征,但它们的miRNA表达特征是不同的。在心脏中稳定检测到的240种miRNA中,有8种在SCH和CCH之间差异表达。具体而言,与CCH和对照病例相比,miR-221在SCH中升高。SCH患者心脏中miR-221的显著升高与致命结局相关。因此,我们的结果表明,miR-221水平升高可能与心脏肥大患者心源性猝死风险增加有关。