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糖尿病血管并发症中的非编码RNA

Noncoding RNAs in diabetes vascular complications.

作者信息

Beltrami Cristina, Angelini Timothy G, Emanueli Costanza

机构信息

National Heart and Lung Institute, Imperial College of London, London, UK.

Royal Surrey County Hospital -NHS Trust, Guilford, UK.

出版信息

J Mol Cell Cardiol. 2015 Dec;89(Pt A):42-50. doi: 10.1016/j.yjmcc.2014.12.014. Epub 2014 Dec 20.

Abstract

Diabetes mellitus is the most common metabolic disorder and is recognised as a dominant health threat of our time. Diabetes induces a widespread damage of the macro- and microvasculature in different organs and tissues and disrupts the endogenous vascular repair mechanisms, thus causing diffuse and severe complications. Moreover, diabetic patients respond poorly to surgical interventions aiming to "revascularise" (i.e., to restore blood flow supply) the ischemic myocardium or lower limbs. The molecular causes underpinning diabetes vascular complications are still underappreciated and druggable molecular targets for therapeutic interventions have not yet clearly emerged. Moreover, diabetes itself and diabetes complications are often silent killers, requiring new prognostic, diagnostic and predictive biomarkers for use in the clinical practice. Noncoding RNA (ncRNAs) are emerging as new fundamental regulators of gene expression. The small microRNAs (miRNAs, miRs) have opened the field capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers. More recently, long ncRNAs (lncRNAs) have started to be actively investigated, leading to first exciting reports, which further suggest their important and yet largely unexplored contribution to vascular physiology and disease. This review introduces the different ncRNA types and focuses at the ncRNA roles in diabetes vascular complications. Furthermore, we discuss the potential value of ncRNAs as clinical biomarkers, and we examine the possibilities for therapeutic intervention targeting ncRNs in diabetes. This article is part of a Special Issue titled: Non-coding RNAs.

摘要

糖尿病是最常见的代谢紊乱疾病,被认为是我们这个时代主要的健康威胁。糖尿病会导致不同器官和组织的大血管和微血管广泛受损,并破坏内源性血管修复机制,从而引发弥漫性和严重并发症。此外,糖尿病患者对旨在使缺血心肌或下肢“血管再通”(即恢复血流供应)的手术干预反应不佳。导致糖尿病血管并发症的分子机制仍未得到充分认识,用于治疗干预的可成药分子靶点也尚未明确出现。此外,糖尿病本身及其并发症往往是隐匿的杀手,需要新的用于临床实践的预后、诊断和预测生物标志物。非编码RNA(ncRNAs)正在成为基因表达的新的重要调节因子。小的微小RNA(miRNAs,miRs)开启了这一领域,因其有可能成为新的治疗靶点而吸引了基础科学家和临床科学家的关注。最近,长链非编码RNA(lncRNAs)也开始受到积极研究,产生了首批令人兴奋的报告,进一步表明它们对血管生理学和疾病具有重要但在很大程度上尚未被探索的作用。本综述介绍了不同类型的ncRNA,并重点阐述了ncRNA在糖尿病血管并发症中的作用。此外,我们讨论了ncRNAs作为临床生物标志物的潜在价值,并探讨了针对糖尿病中ncRNAs进行治疗干预的可能性。本文是名为“非编码RNA”的特刊的一部分。

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