Final Report Summary - CARDIOEPIGEN (Epigenetics and microRNAs in Myocardial Function and Disease)
Epigenetics studies how chromatin – the complex of DNA and histones, the proteins around which DNA is wound – is modified. Opening and closing of chromatin are associated with permissive or inhibitory modes for copying the genome into RNA; in doing so, epigenetic modifications control the expression of genes, which ultimately determine the phenotype of the cell. The importance of epigenetics is reflected by the evidence that genetics alone does not completely account for phenotype. As a matter of fact, environmental factors – which if referred to a disease could be defined as risk factors – reverberate their effects on gene expression in various cell types through complex cascades of events which eventually end up on the chromatin, modulating its state by opening or closing it. Whether and how risk factors such as high blood pressure, atherosclerosis or ischemia lead to chromatin modification, and through which mechanisms they act, represented the topic of this proposal. We first identified the genes modified by pathogenic noxae in the main cell types of the cardiovascular systems; then, we studied the major histone modifications leading to their modulation, unravelling the causal link between the two events. We identified the key players of epigenetic modifications by virtue of genetically modified mice in which the candidate gene was deleted, defining the consequences on disease development. We focused also on RNA molecules known as non-coding RNA, that are not translated into proteins and that were thought to be transcribed from “junk”, useless DNA, but that are now known to be important regulators of gene expression, sometimes acting as epigenetic regulators. We have identified a few of these molecules in cardiac and vascular cells and defined their role in disease processes. As some of these non-coding RNAs – the smallest of which are known as microRNA – are secreted into biological fluids, they can be measured. We demonstrated that in some cardiac pathologies, microRNAs or containers that include them, called microvescicles, can be used as biomarkers of disease, giving precious information on disease status or prognosis.
In conclusion, our research has advanced the current knowledge on the role of epigenetics in cardiovascular diseases, opening new avenues for disease diagnosis and treatment.
In conclusion, our research has advanced the current knowledge on the role of epigenetics in cardiovascular diseases, opening new avenues for disease diagnosis and treatment.