Diesel Exhaust Inhalation Exposure Induces Pulmonary Arterial Hypertension In Mice

Air pollution has become a serious problem in developing countries and has been associated with cardiovascular diseases.Pulmonary arterial hypertension(PAH)is one of the most disastrous vascular diseases,which results in right ventricular failure and death.Diesel exhaust(DE)is one of the main sources of urban air pollution.So far,little data regarding the effects of DE inhalation exposure on PAH is available.It's necessary to research the effect of DE on PAH in mice.In this study,we set up the DE inhalation exposure system,and the diluted DE with filtered air was supplied to the exposure chamber with the flow rate of 40 L/min.The concentrations of total suspended particulates(TSP),NO,NO2,CO and SO2 were 345±33.78?g/m3,236,67±22.75?g/m3,350±30.80?g/m3,11.67±1.71mg/m3 and 14.33±1.15?g/m3,respectively.Male 8-week-old ICR mice were housed in whole-body-exposure chambers and the right ventricular systolic pressure right ventricular systolic pressure(RVSP),morphological changes of right ventricle and pulmonary arterial,the proliferation of vascular smooth muscle cells(VSMCs),apoptosis of endothelial cells in pulmonary artery as well as the pro-inflammatory cytokines were measured after exposure.In this study,we found that DE inhalation induced PAH-phenotype accompanied with increased RVSP,right ventricle hypertrophy and pulmonary arterial thickening.DE exposure induced the proliferation of VSMCs and apoptosis of endothelial cells in pulmonary artery.DE inhalation exposure induced an accumulation of CD45+lymphocytes and CD68+ macrophages surrounding and infiltrating pulmonary arteriole.The levels of pro-inflammatory cytokines tumor necrosis factor(TNF-a),interleukin-6(IL-6)and IL-13 produced by T helper 17(Thl7)and Th2 cells were markedly elevated in lung tissues of mice after DE inhalation exposure.Our findings suggest DE exposure may induce PAH by activating Th17-skewed and Th2-droved responses that stimulating VSMCs proliferation and inducing endothelial cell apoptosis by the production of multifunctional pro-inflammatory cytokines,especially IL-6 and TNF-a.In summary,we found that the effect of DE on the production of PAH can't be ignored.Considering the adverse impact of air pollution on health care,it is imperative to understand air pollution-induced susceptibility of progressive cardiopulmonary disease,such as PAH,and also elucidate critical mechanistic pathways which mediate pulmonary artery vascular remodeling and may serve as targets for preventive measures.It is of great significance to prevent and control diseases induced by air pollution..