Repeat dose exposure of PM(2.5) triggers the disseminated intravascular coagulation (DIC) in SD rats

Epidemiological evidence suggests that fine particulate matter (PM(2.5)) in air pollution promotes the formation of deep venous thrombosis. However, no evidence is available on the effects of PM(2.5) lead to disseminated intravascular coagulation (DIC). For the first time, this study explored the effects of PM(2.5) on DIC via coagulation disorders in vivo. SD rats received intratracheal instillation of PM(2.5) once every three days for one month. Doppler ultrasound showed that the pulmonary valve (PV) and aortic valve (AV) peak flow were decreased after exposure to PM(2.5). Fibrin deposition and bleeding were observed in lung tissue and vascular endothelial injury was found after exposure to PM(2.5). Expression of thrombomodulin (TM) in vessel was downregulated after PM(2.5)-treated, whereas the levels of proinflammatory factors and adhesion molecules (IL-6, IL-1β, CRP, ICAM-1 and VCAM-1) were markedly elevated after exposure to PM(2.5). Tissue factor (TF) and the coagulation factor of FXa were increased, while vWF was significantly lowered induced by PM(2.5). Thrombin-antithrombin complex (TAT) and fibrinolytic factor (t-PA) were elevated, while there was no significantly change in the expression of anticoagulant factors (TFPI and AT-III). To clarify the relationship between PM(2.5) and DIC, we examined the general diagnostic indices of DIC: PM(2.5) prolonged PT and increased the expression of D-dimer but decreased platelet count and fibrinogen. In addition, the gene levels of JAK1 and STAT3 showed an upward trend, whereas there was little effect on JAK2 expression. And inflammatory factors (IL-6, IL-1β and TNF) in blood vessels of were up-reglated in PM(2.5)-treated rats. In summary, our results found that PM(2.5) could induce inflammatory response, vascular endothelial injury and prothrombotic state, eventually resulted in DIC. It will provide new evidence for a link between PM(2.5) and cardiovascular disease.