Melatonin ameliorates PM(2.5)‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Fine particulate matter (PM(2.5)) exposure is correlated with the risk of developing cardiac fibrosis. Melatonin is a major secretory product of the pineal gland that has been reported to prevent fibrosis. However, whether melatonin affects the adverse health effects of PM(2.5) exposure has not been investigated. Thus, this study was aimed to investigate the protective effect of melatonin against PM(2.5)‐accelerated cardiac fibrosis. The echocardiography revealed that PM(2.5) had impaired both systolic and diastolic cardiac function in ApoE(−/−) mice. Histopathological analysis demonstrated that PM(2.5) induced cardiomyocyte hypertrophy and fibrosis, particularly perivascular fibrosis, while the melatonin administration was effective in alleviating PM(2.5)‐induced cardiac dysfunction and fibrosis in mice. Results of electron microscopy and confocal scanning laser microscope confirmed that melatonin had restorative effects against impaired mitochondrial ultrastructure and augmented mitochondrial ROS generation in PM(2.5)‐treated group. Further investigation revealed melatonin administration could significantly reverse the PM(2.5)‐induced phenotypic modulation of cardiac fibroblasts into myofibroblasts. For the first time, our study found that melatonin effectively alleviates PM(2.5)‐induced cardiac dysfunction and fibrosis via inhibiting mitochondrial oxidative injury and regulating SIRT3‐mediated SOD2 deacetylation. Our findings indicate that melatonin could be a therapy medicine for prevention and treatment of air pollution‐associated cardiac diseases.