Abstract

Plasma RNA Signatures of Cardiac Remodeling in Heart Failure Play a Role in Disease Pathogenesis

Saumya Das, Assistant Professor, Harvard Medical School

In the modern era of revascularization, acute mortality from coronary artery disease has decreased. However, adverse cardiac remodeling associated with ischemic heart disease combined with the explosion of cardiometabolic diseases has led to an epidemic of heart failure. There is a large unmet need to discover novel prognostic biomarkers and functional mediators of cardiac remodeling that may be exploited for novel therapies. Plasma extracellular microRNAs have been characterized as diagnostic biomarkers in cardiovascular diseases. Our work has identified plasma microRNA signatures of cardiac remodeling in patients with chronic heart failure and in patients post myocardial infarction. Bioinformatics and network analyses combined with experimental work has demonstrated that the microRNA components of these signatures are highly interconnected and regulate pathways of inflammation, cell growth and fibrosis. Finally, the use of next generation sequencing techniques to expand the repertoire the plasma RNA biomarkers has identified non-miRNA small RNAs, including snoRNAs, Y-RNAs and tRNA fragments as possible novel biomarkers of cardiovascular diseases.