Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice
Abstract Background Cardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function. The purpose of the study is to determine whether the PM2.5-induced cardiac dysfunction is age-dependent and whether the adverse effects can be...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12989-018-0264-2 |
| _version_ | 1811287884744884224 |
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| author | Guohua Qin Jin Xia Yingying Zhang Lianghong Guo Rui Chen Nan Sang |
| author_facet | Guohua Qin Jin Xia Yingying Zhang Lianghong Guo Rui Chen Nan Sang |
| author_sort | Guohua Qin |
| collection | DOAJ |
| description | Abstract Background Cardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function. The purpose of the study is to determine whether the PM2.5-induced cardiac dysfunction is age-dependent and whether the adverse effects can be restored after PM2.5 exposure withdrawal. Methods Female C57BL/6 mice at different ages (4-week-old, 4-month-old, and 10-month-old) received oropharyngeal aspiration of 3 mg/kg b.w. PM2.5 every other day for 4 weeks. Then, 10-month-old and 4-week-old mice were exposed to PM2.5 for 4 weeks and withdrawal PM2.5 1 or 2 weeks. Heart rate and systolic blood pressure were measured using a tail-cuff system. Cardiac function was assessed by echocardiography. Left ventricles were processed for histology to assess myocardial fibrosis. ROS generation was detected by photocatalysis using 2′,7′-dichlorodihydrofluorescein diacetate (DCFHDA). The expression of cardiac fibrosis markers (Col1a1, Col3a1) and possible signaling molecules, including NADPH oxidase 4 (NOX-4), transforming growth factor β1 (TGFβ1), and Smad3, were detected by qPCR and/ or Western blot. Results PM2.5 exposure induced cardiac diastolic dysfunction of mice, elevated the heart rate and blood pressure, developed cardiac systolic dysfunction of 10-month-old mice, and caused fibrosis in both 4-week-old and 10-month-old mice. PM2.5 exposure increased the expression of Col1a1, Col3a1, NOX-4, and TGFβ1, activated Smad3, and generated more reactive oxygen species in the myocardium of 4-week-old and 10-month-old mice. The withdrawal from PM2.5 exposure restored blood pressure, heart rate, cardiac function, expression of collagens, and malonaldehyde (MDA) levels in hearts of both 10-month-old and 4-week-old mice. Conclusion Juvenile and older mice are more sensitive to PM2.5 than adults and suffer from cardiac dysfunction. PM2.5 exposure reversibly elevated heart rate and blood pressure, induced cardiac systolic dysfunction of older mice, and reversibly induced fibrosis in juvenile and older mice. The mechanism by which PM2.5 exposure resulted in cardiac lesions might involve oxidative stress, NADPH oxidase, TGFβ1, and Smad-dependent pathways. |
| first_indexed | 2024-04-13T03:27:17Z |
| format | Article |
| id | doaj.art-77b44a0de6af4fd3a9f96628c2cd6c7c |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-04-13T03:27:17Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-77b44a0de6af4fd3a9f96628c2cd6c7c2022-12-22T03:04:37ZengBMCParticle and Fibre Toxicology1743-89772018-06-0115111410.1186/s12989-018-0264-2Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female miceGuohua Qin0Jin Xia1Yingying Zhang2Lianghong Guo3Rui Chen4Nan Sang5College of Environment and Resource, Research Center of Environment and Health, Shanxi UniversityCollege of Environment and Resource, Research Center of Environment and Health, Shanxi UniversityCollege of Environment and Resource, Research Center of Environment and Health, Shanxi UniversityState Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of SciencesCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety& CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Ambient Particles Health Effects and PreventionTechniques, National Center for Nanoscience & Technology of ChinaCollege of Environment and Resource, Research Center of Environment and Health, Shanxi UniversityAbstract Background Cardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function. The purpose of the study is to determine whether the PM2.5-induced cardiac dysfunction is age-dependent and whether the adverse effects can be restored after PM2.5 exposure withdrawal. Methods Female C57BL/6 mice at different ages (4-week-old, 4-month-old, and 10-month-old) received oropharyngeal aspiration of 3 mg/kg b.w. PM2.5 every other day for 4 weeks. Then, 10-month-old and 4-week-old mice were exposed to PM2.5 for 4 weeks and withdrawal PM2.5 1 or 2 weeks. Heart rate and systolic blood pressure were measured using a tail-cuff system. Cardiac function was assessed by echocardiography. Left ventricles were processed for histology to assess myocardial fibrosis. ROS generation was detected by photocatalysis using 2′,7′-dichlorodihydrofluorescein diacetate (DCFHDA). The expression of cardiac fibrosis markers (Col1a1, Col3a1) and possible signaling molecules, including NADPH oxidase 4 (NOX-4), transforming growth factor β1 (TGFβ1), and Smad3, were detected by qPCR and/ or Western blot. Results PM2.5 exposure induced cardiac diastolic dysfunction of mice, elevated the heart rate and blood pressure, developed cardiac systolic dysfunction of 10-month-old mice, and caused fibrosis in both 4-week-old and 10-month-old mice. PM2.5 exposure increased the expression of Col1a1, Col3a1, NOX-4, and TGFβ1, activated Smad3, and generated more reactive oxygen species in the myocardium of 4-week-old and 10-month-old mice. The withdrawal from PM2.5 exposure restored blood pressure, heart rate, cardiac function, expression of collagens, and malonaldehyde (MDA) levels in hearts of both 10-month-old and 4-week-old mice. Conclusion Juvenile and older mice are more sensitive to PM2.5 than adults and suffer from cardiac dysfunction. PM2.5 exposure reversibly elevated heart rate and blood pressure, induced cardiac systolic dysfunction of older mice, and reversibly induced fibrosis in juvenile and older mice. The mechanism by which PM2.5 exposure resulted in cardiac lesions might involve oxidative stress, NADPH oxidase, TGFβ1, and Smad-dependent pathways.http://link.springer.com/article/10.1186/s12989-018-0264-2Particulate matterCardiacFibrosisReversibleDifferent age |
| spellingShingle | Guohua Qin Jin Xia Yingying Zhang Lianghong Guo Rui Chen Nan Sang Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice Particle and Fibre Toxicology Particulate matter Cardiac Fibrosis Reversible Different age |
| title | Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice |
| title_full | Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice |
| title_fullStr | Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice |
| title_full_unstemmed | Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice |
| title_short | Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice |
| title_sort | ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice |
| topic | Particulate matter Cardiac Fibrosis Reversible Different age |
| url | http://link.springer.com/article/10.1186/s12989-018-0264-2 |
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