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.

中文翻译：

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褪黑激素通过调节线粒体氧化还原稳态来改善 PM2.5 诱导的心脏血管周围纤维化。


细颗粒物 (PM _2.5 ) 暴露与发生心脏纤维化的风险相关。褪黑激素是松果体的主要分泌产物，据报道可以预防纤维化。然而，褪黑激素是否会影响 PM _2.5暴露对健康的不利影响尚未得到研究。因此，本研究旨在探讨褪黑激素对 PM _2.5加速心脏纤维化的保护作用。超声心动图显示，PM _2.5损害了 ApoE ^−/−小鼠的心脏收缩和舒张功能。组织病理学分析表明，PM _2.5诱导心肌细胞肥大和纤维化，特别是血管周围纤维化，而褪黑激素给药可有效缓解 PM _2.5诱导的小鼠心脏功能障碍和纤维化。电子显微镜和共焦扫描激光显微镜的结果证实，褪黑素对 PM _2.5治疗组受损的线粒体超微结构具有恢复作用，并增加线粒体 ROS 的产生。进一步的研究表明，褪黑素给药可以显着逆转 PM _2.5诱导的心肌成纤维细胞向肌成纤维细胞的表型调节。我们的研究首次发现褪黑素通过抑制线粒体氧化损伤和调节SIRT3介导的SOD2脱乙酰化来有效缓解PM _2.5引起的心脏功能障碍和纤维化。我们的研究结果表明，褪黑激素可以作为预防和治疗与空气污染相关的心脏病的治疗药物。