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

TY - JOUR

T1 - Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives

AU - Poller, Wolfgang

AU - Dimmeler, Stefanie

AU - Heymans, Stephane

AU - Zeller, Tanja

AU - Haas, Jan

AU - Karakas, Mahir

AU - Leistner, David-Manuel

AU - Jakob, Philipp

AU - Nakagawa, Shinichi

AU - Blankenberg, Stefan

AU - Engelhardt, Stefan

AU - Thum, Thomas

AU - Weber, Christian

AU - Meder, Benjamin

AU - Hajjar, Roger

AU - Landmesser, Ulf

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - Biomarkers/blood

KW - Cardiovascular Diseases/blood

KW - Gene Silencing

KW - Humans

KW - MicroRNAs/blood

KW - Molecular Targeted Therapy

KW - Precision Medicine

KW - Prognosis

KW - RNA, Long Noncoding/blood

KW - RNA, Small Interfering/therapeutic use

KW - RNA, Untranslated/antagonists & inhibitors

KW - Translational Medical Research

U2 - 10.1093/eurheartj/ehx165

DO - 10.1093/eurheartj/ehx165

M3 - SCORING: Review article

C2 - 28430919

VL - 39

SP - 2704

EP - 2716

JO - EUR HEART J

JF - EUR HEART J

SN - 0195-668X

IS - 29

ER -