Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice

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 PM(2.5)-induced cardiac dysfunction is age-dependent and whether the adverse effects can be restored after PM(2.5) 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. PM(2.5) every other day for 4 weeks. Then, 10-month-old and 4-week-old mice were exposed to PM(2.5) for 4 weeks and withdrawal PM(2.5) 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: PM(2.5) 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. PM(2.5) 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 PM(2.5) 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 PM(2.5) than adults and suffer from cardiac dysfunction. PM(2.5) 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 PM(2.5) exposure resulted in cardiac lesions might involve oxidative stress, NADPH oxidase, TGFβ1, and Smad-dependent pathways. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12989-018-0264-2) contains supplementary material, which is available to authorized users.