Air Fine Particulate Matter Induces Reversibly Myocardial Hypertrophy In Mice

With the development of Chinese economy and modernization,the problem of air pollution,which has an impact on environment and health,has become the main topic of social and scientific research.Among various air pollutants,atmospheric fine particulate matter(PM_2.5)is one of the important factors that cause cardiovascular disease?CVD?.The health effects of PM_2.5on CVD have attracted wide attention from the society and the public.Myocardial hypertrophy as a powerful independent predictor of CVD,it is of great scientific significance to study the effect of PM_2.5 on myocardial hypertrophy in the aspects of exposure effect and protective therapy.Firstly,we prepared PM_2.5 suspension from four seasons,and exposed H9C2 cells to detect the mRNA transcription level of atrial natriuretic peptide?ANP?.Winter was determined to be the season with the most significant toxic effect.Then,H9C2 cells were exposed to different concentrations of winter PM_2.5 suspension.The mRNA transcription level of ANP,?-myosin heavy chain??-MHC?and matrix metalloproteinase?MMPs?were detected.It was found that there was a significant dose-effect relationship.Finally,the addition of N-acetylcysteine?NALC?effectively alleviated PM_2.5-induced myocardial hypertrophy.We further studied the individual differences of the effects of PM_2.5 on myocardial hypertrophy in mice of different ages,and explored the possible molecular mechanisms of this effect through the exposure of mice to PM_2.5 from different cities.Winter PM_2.5 resulted in a significant decrease in the nuclear mass ratio,a significant increase in mRNA transcription level of interleukin-6?IL-6?in 4-week and 10-month-old mice,and a significant increase in mRNA level of ANP and?-MHC only in10-month-old mice.Winter PM_2.5 exposure from Taiyuan reduced the nuclear mass ratio,and significantly increased mRNA transcription level of ANP,?-MHC,transforming growth factor?1?TGF?1?and IL-6 in 10-month-old mice.The results of correlation analysis showed that the mRNA transcription level of cardiac hypertrophy marker gene ANP,?-MHC was positively correlated with the concentration of Zn and AC.The mRNA transcription level of ANP,?-MHC,MMP2,MMP9 and the pathway protein expression level of IL-6,Janus kinase 2?JAK2?and phosphorylated signal transduction and activator of transcription 3?STAT3?was significantly higher than that of the control group.Finally,we explored whether myocardial hypertrophy induced by PM_2.5 exposure was reversible.After exposure to PM_2.5 for 4weeks,the nuclear mass ratio of cardiac myocytes in aged mice decreased significantly,and mRNA transcription levels of ANP,?-MHC,MMP2 and MMP9,and the protein levels of TGF?1 and MMP2 increased significantly.After 1 week of recovery,the nuclear mass ratio still decreased significantly,the protein levels of TGF?1 and MMP2 increased significantly,and the mRNA transcription level of related genes returned to the normal state.After2 weeks of recovery,the mRNA and protein levels of myocardial hypertrophy-associated genes in mice were not significantly different compared with the control group.In conclusion,children and elderly mice were more sensitive to PM_2.5.The occurrence of myocardial hypertrophy in the aged mice is induced by winter PM_2.5 exposure.Compared with the three cities in Beijing,Hangzhou and Guangzhou,the effect of Taiyuan PM_2.5 is more significant,the occurrence of this effect is highly correlated with the concentration of Zn and AC in PM_2.5 and its molecular mechanism may be involved in the IL-6/JAK2/STAT3 signaling pathway.And the myocardial hypertrophy effect of the 2-week recovery period can be recovered to the normal state after the exposure of the PM_2.5,and the effect of the PM_2.5-induced myocardial hypertrophy injury is reversible.