Advances in RNA-sequencing techniques have led to the discovery of thousands of non-coding transcripts with unknown function. There are several types of non-coding linear RNAs such as microRNAs (miRNA) and long non-coding RNAs (lncRNA), as well as circular RNAs (circRNA) consisting of a closed continuous loop. This review guides the reader through important aspects of non-coding RNA biology. This includes their biogenesis, mode of actions, physiological function, as well as their role in the disease context (such as in cancer or the cardiovascular system). We specifically focus on non-coding RNAs as potential therapeutic targets and diagnostic biomarkers.

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Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches

Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish

In recent years, prominent roles for microRNAs (miRNAs) have been uncovered in several cardiovascular disorders. The ability to therapeutically manipulate miRNA expression and function through systemic or local delivery of miRNA inhibitors, referred to as antimiRs, has triggered enthusiasm for miRNAs as novel therapeutic targets. Here, we focus on the pharmacokinetic and pharmacodynamic properties of current antimiR designs and their relevance to cardiovascular indications, and evaluate the opportunities and obstacles associated with this new therapeutic modality.

MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles

Prospective study on circulating MicroRNAs and risk of myocardial infarction

Heart failure (HF) is a leading cause of morbidity and mortality in the United States. Despite a number of important therapeutic advances for the treatment of symptomatic HF,1 the prevalence, mortality, and cost associated with HF continue to grow in the United States and other developed countries. Given the aging of our population and the prevalence of diseases such as diabetes mellitus and hypertension that predispose patients to this syndrome, it is possible that HF prevalence will increase in the next decade. Current treatments primarily slow the progression of this syndrome, and there is a need to develop novel preventative and reparative therapies. Development of these novel HF therapies requires testing of the putative therapeutic strategies in appropriate HF animal models.

The purposes of this scientific statement are to define the distinctive clinical features of the major causes of HF in humans and to recommend those distinctive pathological features of HF in humans that should be present in an animal model being used to identify fundamental causes of HF or to test preventative or reparative therapies that could reduce HF morbidity and mortality.

HF is a clinical syndrome with primary symptoms including dyspnea, fatigue, exercise intolerance, and retention of fluid in the lungs and peripheral tissues. The causes of HF are myriad, but the common fundamental defect is a decreased ability of the heart to provide sufficient cardiac output to support the normal functions of the tissues because of impaired filling and/or ejection of blood.

HF is a significant health burden in both the developed world and in emerging nations. In the United States, over a half million new diagnoses of HF occur each year, and the prevalence is 5.8 million individuals >20 years of age.1 HF has a substantial societal burden, with yearly costs in the United …

Animal Models of Heart Failure A Scientific Statement From the American Heart Association

Background—Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. Methods and Results—Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2–associated death promoter) and Sirtuin...

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MicroRNA-24 Regulates Vascularity After Myocardial Infarction

Jan Fiedler, PhD; Virginija Jazbutyte, PhD; Bettina C. Kirchmaier, PhD; Shashi K. Gupta, MSc;Johan Lorenzen, MD; Dorothee Hartmann, MSc; Paolo Galuppo, PhD; Susanne Kneitz, PhD;John T.G. Pena, MD; Cherin Sohn-Lee, PhD; Xavier Loyer, PhD; Juergen Soutschek, PhD;Thomas Brand, PhD; Thomas Tuschl, PhD; Joerg Heineke, MD; Ulrich Martin, PhD;Stefan Schulte-Merker, PhD; Georg Ertl, MD; Stefan Engelhardt, MD, PhD;Johann Bauersachs, MD; Thomas Thum, MD, PhD

Juergen Soutschek

Papers

MicroRNA-24 Regulates Vascularity After Myocardial Infarction

Heart Failure MicroRNA-24 Regulates Vascularity After Myocardial Infarction