TY - JOUR
T1 - Extracellular vesicle-driven information mediates the long-term effects of particulate matter exposure on coagulation and inflammation pathways
AU - Pavanello, Sofia
AU - Bonzini, Matteo
AU - Angelici, Laura
AU - Motta, Valeria
AU - Pergoli, Laura
AU - Hoxha, Mirjam
AU - Cantone, Laura
AU - Pesatori, Angela Cecilia
AU - Apostoli, Pietro
AU - Tripodi, Armando
AU - Baccarelli, Andrea
AU - Bollati, Valentina
PY - 2016/9/30
Y1 - 2016/9/30
N2 - Background Continuous exposure to particulate air pollution (PM) is a serious worldwide threat to public health as it coherently links with increased morbidity and mortality of cardiorespiratory diseases (CRD), and of type 2 diabetes (T2D). Extracellular vesicles (EVs) are circular plasma membrane fragments released from human cells that transfer microRNAs between tissues. In the present work it was explored the hypothesis that EVs with their encapsulated microRNAs (EVmiRNAs) contents might mediate PM effects by triggering key pathways in CRD and T2D. Methods Expression of EVmiRNAs analyzed by real-time PCR was correlated with oxidative stress, coagulation and inflammation markers, from healthy steel plant workers (n = 55) with a well-characterized exposure to PM and PM-associated metals. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways regulated by PM-associated EVmiRNAs. Results Increased expression in 17 EVmiRNAs is associated with PM and metal exposure (p < 0.01). Mir-196b that tops the list, being related to 9 different metals, is fundamental in insulin biosynthesis, however three (miR-302b, miR-200c, miR-30d) out of these 17 EVmiRNAs are in turn also related to disruptions (p < 0.01) in inflammatory and coagulation markers. Conclusions The study's findings support the hypothesis that adverse cardiovascular and metabolic effects stemming from inhalation exposures in particular to PM metallic component may be mediated by EVmiRNAs that target key factors in the inflammation, coagulation and glucose homeostasis pathways.
AB - Background Continuous exposure to particulate air pollution (PM) is a serious worldwide threat to public health as it coherently links with increased morbidity and mortality of cardiorespiratory diseases (CRD), and of type 2 diabetes (T2D). Extracellular vesicles (EVs) are circular plasma membrane fragments released from human cells that transfer microRNAs between tissues. In the present work it was explored the hypothesis that EVs with their encapsulated microRNAs (EVmiRNAs) contents might mediate PM effects by triggering key pathways in CRD and T2D. Methods Expression of EVmiRNAs analyzed by real-time PCR was correlated with oxidative stress, coagulation and inflammation markers, from healthy steel plant workers (n = 55) with a well-characterized exposure to PM and PM-associated metals. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways regulated by PM-associated EVmiRNAs. Results Increased expression in 17 EVmiRNAs is associated with PM and metal exposure (p < 0.01). Mir-196b that tops the list, being related to 9 different metals, is fundamental in insulin biosynthesis, however three (miR-302b, miR-200c, miR-30d) out of these 17 EVmiRNAs are in turn also related to disruptions (p < 0.01) in inflammatory and coagulation markers. Conclusions The study's findings support the hypothesis that adverse cardiovascular and metabolic effects stemming from inhalation exposures in particular to PM metallic component may be mediated by EVmiRNAs that target key factors in the inflammation, coagulation and glucose homeostasis pathways.
KW - Cardiorespiratory diseases (CRD)
KW - Coagulation
KW - EV-encapsulated microRNAs (EVmiRNAs)
KW - Extracellular vesicles (EVs)
KW - Inflammation
KW - microRNAs
KW - Particulate air pollution (PM)
KW - Type 2 diabetes (T2D)
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U2 - 10.1016/j.toxlet.2016.08.002
DO - 10.1016/j.toxlet.2016.08.002
M3 - Article
AN - SCOPUS:84989880512
VL - 259
SP - 143
EP - 150
JO - Toxicology Letters
JF - Toxicology Letters
SN - 0378-4274
ER -