Call us at: 1.866.416.4636 | Europe: +800.0751.2020

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

Guohua Qin, Jin Xia, Yingying Zhang, Lianghong Guo, Rui Chen, Nan Sang
Particle and Fibre Toxicology2018
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 dysfunctionof10-month-oldmice, andcausedfibrosisinboth4-week-old and10-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.
Share

Request a Quote or Demo

Contact Us