Air pollution exposure, in particular the particulate matter (PM) component, has been consistently linked to an increased risk of developing acute and chronic cardiovascular diseases (CVD). The SPHERE ("Susceptibility to Particle Health Effects, miRNAs and Exosomes") project was granted by ERC-2011-StG 282413 to examine possible molecular mechanisms underlying the effects of PM exposure in relation to health outcomes. In this project, in particular, we investigated the role exerted by extracellular vesicles (EV) and their miRNA cargo in mediating the cardiovascular effects of PM exposure. EVs might be the ideal candidate to mediate the effects of PM, since they could be potentially produced by the respiratory system, reach the systemic circulation and lead to the development of cardiovascular effects. In the SPHERE study, we confirmed in a population of obese subjects that PM is able to stimulate EV release in plasma and we were able to identify a EV-specific miRNA signature, responsive to PM exposure. One of the most important gaps in our current knowledge regarding PM-related cardiovascular health effects is the identification of susceptible subjects. This identification would provide the groundwork for the development of prevention strategies and of targeted treatments.
The Proof of Concept project VERA (Extracellular VEsicles, miRNAs and particulate Air pollution: developing a new tool to identify subjects with high exposure-associated cardiovascular risk) aims to confirm the commercial and technological feasibility of a tool (VERAKit) for testing EV-specific miRNA expression, in order to identify subjects with an higher susceptibility to PM. VERAkit allows a customized screening strategy aimed at: i) guaranteeing an early diagnosis of possible cardiovascular diseases; ii) minimizing not only the health consequences but also the economic impact deriving from the costs for treatment and the possible loss of working days.
The data produced during the present project supported the feasibility to apply the VeraKit to screen the individual susceptibility to the effect of particulate air pollution. Moreover, the miRNA signature investigated by the VeraKit resulted to be altered also in patients with a major acute cardiovascular event.
The next steps will involve the application of the VeraKit in a prospective investigation, in order to assess its predictive value and to better understand the timing of the molecular process (i.e. how long before the CVD event this specific miRNA signature becomes altered).
