Blood-derived extracellular vesicles isolated from healthy donors exposed to air pollution modulate in vitro endothelial cells behavior

Abstract

The release of Extracellular Vesicles (EVs) into the bloodstream is positively associated with Particulate Matter (PM) exposure, which is involved in endothelial dysfunction and related to increased risk of cardiovascular disease. Obesity modifies the effects of PM exposure on heart rate variability and markers of inflammation, oxidative stress, and acute phase response. We isolated and characterized plasmatic EVs from six healthy donors and confirmed a positive association with PM exposure. We stratified for Body Mass Index (BMI) and observed an increased release of CD61+ (platelets) and CD105+ (endothelium) derived-EVs after high PM level exposure in Normal Weight subjects (NW) and no significant variations in Overweight subjects (OW). We then investigated the ability to activate endothelial primary cells by plasmatic EVs after both high and low PM exposure. NW-high-PM EVs showed an increased endothelial activation, measured as CD105+/CD62e+ (activated endothelium) EVs ratio. On the contrary, cells treated with OW-high-PM EVs showed reduced endothelial activation. These results suggest the ability of NW plasmatic EVs to communicate to endothelial cells and promote the crosstalk between activated endothelium and peripheral cells. However, this capacity was lost in OW subjects. Our findings contribute to elucidate the role of EVs in endothelial activation after PM exposure.

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

“…EVs derived from PM-exposed alveolar epithelial cells fueled inflammatory signaling via inhibitor of the nuclear factor kappa alpha (IκBα)–nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)–vascular cell adhesion protein 1 (VCAM1) axis [ 52 ]. Nevertheless, EVs shed after PM exposure could also mediate crosstalk between EC-immune cells to cope with the inflammatory assault [ 53 ], a response impaired in overweight subjects at increased cardiovascular risk [ 54 ].…”

The impact of environmental contaminants on extracellular vesicles and their key molecular regulators: A literature and database‐driven review

“…In two of these studies, human exposure to PM was characterized by regional air monitors and EVs were isolated from human plasma samples. These studies both showed that EVs were released in a greater concentration after short‐term exposure to high‐level PM compared to low‐level PM after 24 h (Bonzini et al, 2017; Rota et al, 2020). Both studies also identified overweight individuals as a particularly susceptible population.…”

“…In these studies, both adverse and protective effects have been observed. For example, EVs isolated from human plasma with varying PM exposure levels were used to treat primary endothelial cells (Rota et al, 2020). EVs isolated from human plasma with high PM exposure increased endothelial activation, while EVs isolated from human plasma with low PM exposure decreased endothelial activation (Rota et al, 2020).…”

Particulate Matter Exposure and Allergic Rhinitis: The Role of Plasmatic Extracellular Vesicles and Bacterial Nasal Microbiome

“…In this context, plasmatic extracellular vesicles (EVs), which have a critical role in the cross-talk between cells [12][13][14], are a good candidate as mediators of the airway allergic process enhancement [15,16]. Moreover, EVs strongly contribute to the modulation of the inflammatory response after PM exposure, thus enforcing this hypothesis [17][18][19]. Interestingly, EVs represent a conserved communication mechanism between domains of life; indeed they can be released by human (i.e., hEVs) and bacterial cells (i.e., bEVs) into the bloodstream [13,14,20].…”

“…Quantitative multiparameter analysis of flow cytometry data (expressed as 10 3 for 1 mL of plasma) was run using FlowJo software (Tree Star, Inc., Ashland, OR, USA). Antibody gating strategies are reported in the supplementary information (Supplementary Figures S1-S4) and were previously described [17,35].…”