Jilin Provincial Key Laboratory of Animal Embryo Engineering, Department of Animal Biotechnology, College of Animal Science, Jilin University, Changchun 130062, China; Department of Toxicology, School of Public Health, Beihua University, Jilin 132011, Jilin, China; Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy and Hong Qi Hospital, Mudanjiang Medical University, Mudanjiang 157011, China.
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Center for Molecular Medicine, Room 207B, 1664 North. Virginia Street, MS/0575, Reno, NV 89557, USA.
Exp Cell Res. 2018 Apr 1;365(1):119-128. doi: 10.1016/j.yexcr.2018.02.029. Epub 2018 Feb 28.
Heart failure arises from diverse cardiovascular diseases, including hypertension, ischemic disease and atherosclerosis, valvular insufficiency, myocarditis, and contractile protein mutations. MicroRNAs are dysregulated in heart failure, but identification of the specific microRNAs involved remains incomplete. Here, we evaluate miR-25 expression in the peripheral blood from healthy, dilated cardiomyopathy (DCM), remote infarct (OMI), hypertensive heart disease (HHD), and HHD resulting in heart failure (HHDF) using q-PCR. Interestingly, we discovered miR-25 expression in humans is initially decreased at the onset of heart failure but is later increased in end-stage heart failure. We also show that overexpression of miR-25 in normal mice causes cardiomyocyte fibrosis and apoptosis. However, inhibition of miR-25 in normal mice led to activate renin-angiotensin system (RAS) and high blood pressure, mild heart dilation. Notably, the miR-25 cluster knock-out mice was also characterized high blood pressure and no obvious cardiac function alteration. RNA sequencing showed the alteration of miR-25 target genes in angomir-treated mice, including the renin secretion signal related gene. In vitro, cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the Pde3a and Cacnalc untranslated region. In summary, miR-25 expression during different stages of heart disease, offers a new perspective for the role of miR-25 function in heart failure.
心力衰竭源于多种心血管疾病，包括高血压、缺血性疾病和动脉粥样硬化、瓣膜功能不全、心肌炎和收缩蛋白突变。miRNA 在心力衰竭中失调，但涉及的特定 miRNA 的鉴定仍不完整。在这里，我们使用 q-PCR 评估了健康人、扩张型心肌病 (DCM)、陈旧性梗塞 (OMI)、高血压性心脏病 (HHD) 和 HHD 导致心力衰竭 (HHDF) 患者外周血中的 miR-25 表达。有趣的是，我们发现心力衰竭开始时人类的 miR-25 表达最初降低，但随后在心力衰竭终末期增加。我们还表明，在正常小鼠中过表达 miR-25 会导致心肌细胞纤维化和凋亡。然而，在正常小鼠中抑制 miR-25 会导致肾素-血管紧张素系统 (RAS) 激活和高血压、轻度心脏扩张。值得注意的是，miR-25 簇敲除小鼠也表现出高血压和明显的心脏功能改变。RNA 测序显示，在 angomir 处理的小鼠中，miR-25 靶基因发生改变，包括肾素分泌信号相关基因。在体外，共转染 miR-25 拮抗剂抑制了包含 Pde3a 和 Cacnalc 非翻译区的报告构建体中的荧光素酶活性。总之，miR-25 在心脏病不同阶段的表达为 miR-25 在心力衰竭中的功能作用提供了新的视角。
