Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overload
Background: Previous studies have shown a significant correlation between exposure to ambient fine particulate matter (PM2.5) and cardiac fibrosis, yet the precise detrimental effects and underlying mechanisms of PM2.5 exposure on cardiac fibrosis remain incompletely understood. Cardiac remodeling,...
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Elsevier
2025-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325005639 |
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| author | Jinjin Jiang Yang Li Yuping Chen Qin Wu Shibin Ding |
| author_facet | Jinjin Jiang Yang Li Yuping Chen Qin Wu Shibin Ding |
| author_sort | Jinjin Jiang |
| collection | DOAJ |
| description | Background: Previous studies have shown a significant correlation between exposure to ambient fine particulate matter (PM2.5) and cardiac fibrosis, yet the precise detrimental effects and underlying mechanisms of PM2.5 exposure on cardiac fibrosis remain incompletely understood. Cardiac remodeling, a process involving ferroptosis that can be initiated by iron overload, has been implicated in this phenomenon. In this study, we sought to explore the potential mechanism by which ferroptosis contributes to PM2.5-induced cardiac fibrosis. Methods and results: Male C57BL/6 J mice were exposed to ambient PM2.5 by intratracheal instillation twice a week for 12 weeks to establish PM2.5-exposed murine models and cardiomyocytes were used to verify the role of ferroptosis in PM2.5-induced cardiac fibrosis. In this study, it was observed that exposure to PM2.5 resulted in cardiac fibrosis and a significant upregulation of cardiac fibrosis-related markers (TGF-β1, collagen-I and p-Smad3), heme oxygenase 1 (HO-1), and ACSL4 (a biomarker for ferroptosis). Additionally, PM2.5 exposure led to a decrease in heme content, iron overload, increased levels of the lipid peroxidation marker 4-HNE, and a reduction in the ratio of GSH/GSSG and GPX4 (a biomarker for ferroptosis) in murine hearts. Significantly, the use of ferrostatin-1 (an inhibitor of ferroptosis) mitigated PM2.5-induced cardiac fibrosis and decreased the levels of cardiac fibrosis-related markers (TGF-β1, collagen-I and p-Smad3) in murine hearts, indicating the essential role of ferroptosis in the development of cardiac fibrosis. In vitro experiments showed that PM2.5 upregulated the expression of HO-1 protein, promoted iron accumulation, increased 4-HNE levels, and triggered ferroptosis in cardiomyocytes. The inhibition of HO-1 (zinc protoporphyrin 9) and siRNA HO-1 effectively mitigated PM2.5-induced iron overload, ferroptosis, and heme accumulation in cardiomyocytes. Additionally, treatment with ferrostatin-1 markedly decreased the expression levels of cardiac fibrosis-related markers, such as TGF-β1 and p-Smad3. Conclusion: Collectively, our study showed that the activation of ferroptosis/TGF-β1/Smad3 signaling pathway, initiated by heme degradation-induced iron overload in cardiomyocytes, serves as a mechanism in murine models of PM2.5-induced cardiac fibrosis. |
| format | Article |
| id | doaj-art-54a14c0dec784bd3a69bae5ee5a16605 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-54a14c0dec784bd3a69bae5ee5a166052025-08-20T03:53:12ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129711822710.1016/j.ecoenv.2025.118227Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overloadJinjin Jiang0Yang Li1Yuping Chen2Qin Wu3Shibin Ding4School of Public Health and Management, Jiangsu Medical College, Yancheng, Jiangsu Province 224005, PR China; Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Yancheng, Jiangsu Province 224005, PR ChinaSchool of Public Health and Management, Jiangsu Medical College, Yancheng, Jiangsu Province 224005, PR China; Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Yancheng, Jiangsu Province 224005, PR ChinaJiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Yancheng, Jiangsu Province 224005, PR China; Department of Technology, Jiangsu Medical College, Yancheng, Jiangsu Province 224005, PR ChinaJiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Yancheng, Jiangsu Province 224005, PR China; Jiangsu Medical College, Yancheng, Jiangsu Province 224005, PR China; Corresponding author at: Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Yancheng, Jiangsu Province 224005, PR China.School of Public Health and Management, Jiangsu Medical College, Yancheng, Jiangsu Province 224005, PR China; Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Yancheng, Jiangsu Province 224005, PR China; Corresponding author at: School of Public Health and Management, Jiangsu Medical College, Yancheng, Jiangsu Province 224005, PR China.Background: Previous studies have shown a significant correlation between exposure to ambient fine particulate matter (PM2.5) and cardiac fibrosis, yet the precise detrimental effects and underlying mechanisms of PM2.5 exposure on cardiac fibrosis remain incompletely understood. Cardiac remodeling, a process involving ferroptosis that can be initiated by iron overload, has been implicated in this phenomenon. In this study, we sought to explore the potential mechanism by which ferroptosis contributes to PM2.5-induced cardiac fibrosis. Methods and results: Male C57BL/6 J mice were exposed to ambient PM2.5 by intratracheal instillation twice a week for 12 weeks to establish PM2.5-exposed murine models and cardiomyocytes were used to verify the role of ferroptosis in PM2.5-induced cardiac fibrosis. In this study, it was observed that exposure to PM2.5 resulted in cardiac fibrosis and a significant upregulation of cardiac fibrosis-related markers (TGF-β1, collagen-I and p-Smad3), heme oxygenase 1 (HO-1), and ACSL4 (a biomarker for ferroptosis). Additionally, PM2.5 exposure led to a decrease in heme content, iron overload, increased levels of the lipid peroxidation marker 4-HNE, and a reduction in the ratio of GSH/GSSG and GPX4 (a biomarker for ferroptosis) in murine hearts. Significantly, the use of ferrostatin-1 (an inhibitor of ferroptosis) mitigated PM2.5-induced cardiac fibrosis and decreased the levels of cardiac fibrosis-related markers (TGF-β1, collagen-I and p-Smad3) in murine hearts, indicating the essential role of ferroptosis in the development of cardiac fibrosis. In vitro experiments showed that PM2.5 upregulated the expression of HO-1 protein, promoted iron accumulation, increased 4-HNE levels, and triggered ferroptosis in cardiomyocytes. The inhibition of HO-1 (zinc protoporphyrin 9) and siRNA HO-1 effectively mitigated PM2.5-induced iron overload, ferroptosis, and heme accumulation in cardiomyocytes. Additionally, treatment with ferrostatin-1 markedly decreased the expression levels of cardiac fibrosis-related markers, such as TGF-β1 and p-Smad3. Conclusion: Collectively, our study showed that the activation of ferroptosis/TGF-β1/Smad3 signaling pathway, initiated by heme degradation-induced iron overload in cardiomyocytes, serves as a mechanism in murine models of PM2.5-induced cardiac fibrosis.http://www.sciencedirect.com/science/article/pii/S0147651325005639Fine particulate matterCardiac fibrosisFerroptosisHeme oxygenase-1Iron overload |
| spellingShingle | Jinjin Jiang Yang Li Yuping Chen Qin Wu Shibin Ding Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overload Ecotoxicology and Environmental Safety Fine particulate matter Cardiac fibrosis Ferroptosis Heme oxygenase-1 Iron overload |
| title | Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overload |
| title_full | Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overload |
| title_fullStr | Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overload |
| title_full_unstemmed | Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overload |
| title_short | Ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced-iron overload |
| title_sort | ambient fine particulate matter induces cardiac fibrosis through triggering ferroptosis by heme degradation induced iron overload |
| topic | Fine particulate matter Cardiac fibrosis Ferroptosis Heme oxygenase-1 Iron overload |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325005639 |
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