Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives

Wolfgang Poller*, Stefanie Dimmeler, Stephane Heymans, Tanja Zeller, Jan Haas, Mahir Karakas, David-Manuel Leistner, Philipp Jakob, Shinichi Nakagawa, Stefan Blankenberg, Stefan Engelhardt, Thomas Thum, Christian Weber, Benjamin Meder, Roger Hajjar, Ulf Landmesser

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

164 Citations (Web of Science)

Abstract

Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment. Beyond this, ncRNAs are rapidly emgerging as fundamentally novel therapeutics. On a first level, ncRNAs provide novel therapeutic targets some of which are entering assessment in clinical trials. On a second level, new therapeutic tools were developed from endogenous ncRNAs serving as blueprints. Particularly advanced is the development of RNA interference (RNAi) drugs which use recently discovered pathways of endogenous short interfering RNAs and are becoming versatile tools for efficient silencing of protein expression. Pioneering clinical studies include RNAi drugs targeting liver synthesis of PCSK9 resulting in highly significant lowering of LDL cholesterol or targeting liver transthyretin (TTR) synthesis for treatment of cardiac TTR amyloidosis. Further novel drugs mimicking actions of endogenous ncRNAs may arise from exploitation of molecular interactions not accessible to conventional pharmacology. We provide an update on recent developments and perspectives for diagnostic and therapeutic use of ncRNAs in cardiovascular diseases, including atherosclerosis/coronary disease, post-myocardial infarction remodelling, and heart failure.
Original languageEnglish
Pages (from-to)2704–2716
Number of pages13
JournalEuropean Heart Journal
Volume39
Issue number29
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • Cardiovascular diseases
  • Long non-coding RNAs
  • microRNAs
  • Short interfering RNAs
  • Human non-coding genome
  • ACUTE MYOCARDIAL-INFARCTION
  • GENOME-WIDE ASSOCIATION
  • CORONARY-ARTERY-DISEASE
  • CARDIAC GENE-TRANSFER
  • NONSMALL MOLECULE THERAPEUTICS
  • MECHANICAL CIRCULATORY SUPPORT
  • HUMAN EPIGENOME CONSORTIUM
  • CHRONIC HEART-FAILURE
  • IN-VIVO
  • ANTISENSE OLIGONUCLEOTIDES
  • CIRCULATING MICRORNAS
  • ENDOTHELIAL DYSFUNCTION
  • MYOCARDIAL-INFARCTION
  • HEART-FAILURE
  • LDL CHOLESTEROL

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