Susceptibility to particle health effects, miRNA and exosomes: rationale and study protocol of the SPHERE study

Valentina Bollati, Simona Iodice, Chiara Favero, Laura Angelici, Benedetta Albetti, Raquel Cacace, Laura Cantone, Michele Carugno, Tommaso Cavalleri, Barbara De Giorgio, Laura Dioni, Silvia Fustinoni, Mirjam Hoxha, Barbara Marinelli, Valeria Motta, Lorenzo Patrini, Laura Pergoli, Luciano Riboldi, Giovanna Rizzo, Federica Rota, Sabrina Sucato, Letizia Tarantini, Amedea Silvia Tirelli, Luisella Vigna, Pieralberto Bertazzi, Angela Cecilia Pesatori

Despite epidemiological findings showing increased air pollution related cardiovascular diseases (CVD), the knowledge of the involved molecular mechanisms remains moderate or weak. Particulate matter (PM) produces a local strong inflammatory reaction in the pulmonary environment but there is no final evidence that PM physically enters and deposits in blood vessels. Extracellular vesicles (EVs) and their miRNA cargo 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.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.Methods/design: The study population will include 2000 overweight (25 < BMI < 30 kg/cm2) or obese (BMI >= 30 kg/cm2) subjects presenting at the Center for Obesity and Work (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy).Each subject donates blood, urine and hair samples. Extensive epidemiological and clinical data are collected. Exposure to PM is assigned to each subject using both daily PM10 concentration series from air quality monitors and pollutant levels estimated by the FARM (Flexible Air Quality Regional Model) modelling system and elaborated by the Regional Environmental Protection Agency.The recruitment period started in September 2010 and will continue until 2015. At December 31, 2013 we recruited 1250 subjects, of whom 87% lived in the province of Milan.Primary study outcomes include cardiometabolic and respiratory health effects. The main molecular mechanism we are investigating focuses on EV-associated microRNAs.