A Study Of Fine Particulate Matter Induces Cardiac Dysfunction And Fibrosis In Mice Of Different Ages And Its Reversibility

Recently,air pollution has been considered one of the most serious environmental problems around the world,causing adverse health effects to human.Fine particulate matter(PM_2.5),as the main pollutant,has received increasing attention.Epidemiological evidence supports a robust association between exposure to PM_2.5 and morbidity and mortality due to cardiovascular diseases（CVD）.CVD causes millions of people die every year in this plant.So it is meaningful to study the relationship of PM_2.5 and CVD.In the present study,H9C2 cells were treated with PM_2.5 from different seasons for 24 h.The strongest effect of PM_2.5 on collagen expression was observed after winter PM_2.5 treatment.Female C57BL/6 mice at different ages received oropharyngeal aspiration 3 mg/kg.b.w.winter PM_2.5 suspension for 4 weeks.It was observed that winter PM_2.5 exposure altered the heart rate and blood pressure of 10-month-old mice,developed more cardiac dysfunction and fibrosis in 4-week-old and 10-month-old mice.These conditions were accompanied by increases in the expression of collagen I（Col1a1）,collagen III（Col3a1）,NADPH oxidase 4（NOX-4）,and transforming growth factorβ1（TGFβ1）,and Smad activation in the myocardium.Then,10-month-old female C57BL/6 mice were exposed to winter PM_2.5 for 4 weeks,the above indexes were detected at different time points after withdrawal PM_2.5 one day,one week or two weeks.Withdrawal from PM_2.5 exposure one week restored blood pressure,cardiac systolic function.The heart rate,cardiac diastolic function and collagen deposition were restored after withdrawal from PM_2.5 exposure two weeks.Meanwhile,oxidative damage were detected in hearts and lungs.Winter PM_2.5 increased ROS in hearts of 4-week-old and 10-month-old mice.The MDA levels were reversible induced in hearts and lungs.In conclusion,children and elderly mice might be more sensitive to PM_2.5 than adults and may suffer from cardiac dysfunction.PM_2.5 exposure reversibly altered heart rate and blood pressure,induced cardiac dysfunction and fibrosis in aged mice.The mechanism by which PM_2.5 exposure resulted in cardiac lesions might involve oxidative stress,NADPH oxidase,TGFβ1,and Smad-dependent pathways.