DEFINITION OF TRANSCRIPTIONAL LANDSCAPE IN CARDIAC MATURATION AND CARDIAC HYPERTROPHY

Heart failure (HF) is a syndrome resulting from a complex genetic predisposition and multiple environmental factors: it is a leading cause of morbidity and mortality. Specific gene expression patterns are activated in the hypertrophic and failing heart and are thought to contribute to the development of HF. Many regulatory molecules are involved in the control of gene expression: among these, long non-coding RNA (lncRNA) is gaining importance for several cellular process and diseases. However, little is still known about its involvement in HF. Many functions have been attributed to lncRNAs, such as cell proliferation, apoptosis and cell invasion, indicating that they may represent a major regulatory component of the eukaryotic genome. Not surprisingly, lncRNAs have been found implicated in several aspects of cancer, and in many neuronal diseases. Despite this, and the known role of other ncRNAs, such as miRNA, in HF, the function of lncRNAs in this pathologic state has been not studied. Thus, the general hypothesis behind this project is that lncRNAs have an important role in defining gene expression re-programming in HF. Consequently, the overall scientific objective of this proposal is to study the role of lncRNAs in gene transcription regulation accompanying heart failure. To this end, we propose to use high-throughput RNA sequencing (RNA-seq) to identify lncRNAs that are modulated in cardiomyocytes during HF. In order do to this, we performed RNA-seq on cardiomyocytes isolated from mice after 1, 2, 4 and 7 days of transverse aortic constriction (TAC) and from sham-operated mice. The importance of this study lies not only in the furthering of our understanding of the pathological mechanisms leading HF, but aims to generate – in the light of recent progress in RNA-based therapeutic strategies – data that may be instrumental to the development of improved therapeutic strategies for this increasingly frequent pathology.