Abstract
BackgroundCardiovascular 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.MethodsFemale 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.ResultsPM2.5 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.ConclusionJuvenile 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.
Highlights
Cardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function
Exposure to PM2.5 elevates heart rate and systolic blood pressure of 10-month-old mice For the heart rate of 4-week-old mice, 4 weeks of PM2.5 exposure caused a significant increase compared with pre-exposure but a non-significant increase compared with age-matched control group (Fig. 1a)
The results of our present study provide evidence that PM2.5 aspiration induced cardiac dysfunction and fibrosis in 4-week-old and 10-month-old mice, and the adverse effects could be resolved after PM2.5 exposure withdrawal
Summary
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. Recent studies have demonstrated that exposure to PM2.5 promotes systolic and diastolic dysfunction [7, 8], and exposure to carbon black impairs cardiac function in senescent mice [9]. Exposure to diesel exhaust or PM2.5 during early life can cause significant cardiovascular dysfunction in adulthood [10, 11]. The susceptibility of individuals of different ages to cardiovascular disease caused by PM2.5 exposure has not been investigated. We hypothesized that PM2.5 exposure may induce different effects in different life phases, such as juvenile, adult, and older subpopulations
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