Objective In spite of more than two decades of mechanistic research, the recent statement of air pollution and Cardiovascular Diseases (CVD) from the American Heart Association remarked that at front of high degree of consistency of the epidemiology findings showing increased air pollution related CVD risk, the evidence on intermediate mechanisms remains moderate or weak. Exosomes might be the ideal candidate to mediate the effects of air pollution, since potentially they could be produced by the respiratory system, reach the systemic circulation and lead to the development of endothelial dysfunction.The main object of our proposal is to determine whether exposure to air particles and PM-associated metals can modify exosomes (as quantity, size, membrane molecules, procoagulant activity and miRNAs content) in plasma of human subjects and to investigate whether these alterations may be linked to CVD risk factors and outcomes. The study population will include 2000 overweighed/obese subjects presenting at the Center for Obesity and Weight Control, Milan. Obese subjects have been shown to be particularly susceptible to the effects of air pollution. Exposure to air pollutants will be assessed using: a) ambient concentrations of particulate and gaseous air pollutants; b) geographical information and modelling; c) road density and traffic intensity data; d) Metals determination in urine and hair; e) Personal passive samplers (to measure PM), on a subgroup of subjects (n=200). To identify altered exosome-associated miRNAs , we will follow a two-stage, split sample study design: a discovery stage involving OpenArray miRNA expression profiling (on 1000 subjects) and a replication stage involving a real time analysis of the top 10 miRNAs. We will integrate the human study with an in-vitro model using a system made of paired cell cultures (A549 lung/ granulocytes and endothelial cells) to clarify if exosomes produced by lung/granulocytes can directly interact with endothelial cells. Fields of science medical and health sciencesclinical medicinepneumologynatural sciencesbiological sciencescell biologyengineering and technologyenvironmental engineeringair pollution engineeringmedical and health sciencesclinical medicinecardiologycardiovascular diseasesnatural sciencesearth and related environmental sciencesenvironmental sciencespollution Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator UNIVERSITA DEGLI STUDI DI MILANO Address Via festa del perdono 7 20122 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments Administrative Contact Manuela Marconi (Ms.) Principal investigator Valentina Bollati (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI MILANO Italy EU contribution € 1 444 742,00 Address Via festa del perdono 7 20122 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments Administrative Contact Manuela Marconi (Ms.) Principal investigator Valentina Bollati (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
