Ricerc@Sapienza

Tobacco cigarette, a serious health problem affecting millions of people including young subjects, is a main cause of cardiovascular complications. From a biological standpoint, reduced bioavailability of nitric oxide, increased oxidative stress and adhesion molecules and dysfunctional immune response, generate an inflammatory and progressively chronic microenvironment responsible of altering endothelial permeability barrier and vascular system. So far, precise molecular mechanisms accompanying the aforementioned phenomena have not been fully elucidated. Likewise, circulating markers to early detect vascular changes after smoking need to be explored and validated. Accordingly, smoking can be conceived as an epigenetic factor, contributing to modify interaction with chromatin and gene expression. Accumulating evidence indicates that circulating microRNAs, considered as epigenetic players, reflect the pathophysiological scenario of disease in patients. However, the specific impact of smoking on circulating miRNAs associated to cardiovascular disorders requires investigation. Our preliminary results show that among several endothelial-associated miRNAs quantified in healthy subjects, miR-155 results significantly increased in serum just after 30 minutes. miR-155 is released in vitro by endothelial cells (HUVEC) in response to stress (hydrogen peroxide) without evidence of cell death. The administration of mimic miR-155 increases inflammatory markers, impairing angiogenesis and cell survival in HUVEC accompanied by downregulation of VEGF and eNOS protein levels. Based on these results, here we aim to demonstrate the cause-effect association between increase of miR-155 and endothelial function impairment in acute and chronic conditions of smoking cigarettes. We will also dissect the reversible aspect of this epigenetic molecular mechanism, seeking for the impact of miR-155 as a potential biomarker of early biological effects ascribable to smoke on endothelial damage