However, the mechanisms underlying the cardiac fibrosis effects of PM 2.5 are unclear. Transforming growth factor β1 (TGFβ1), a critical regulator of fibroblast phenotype and function, acts through Smad-dependent or independent pathways. In addition to the loss of contractile capacity, inhalation of PM 2.5 is associated with adverse ventricular remodeling and worsening of cardiac fibrosis. It is characterized by the adverse accumulation of collagen and other extracellular matrix proteins. Cardiac fibrosis is a common phenotype found in several cardiac diseases, including myocardial infarction and heart failure. Numerous investigations have elucidated potential biological mechanisms, whereby exposure to PM 2.5 may modulate disease susceptibility, including the progression of atherosclerosis, inflammation, thrombosis, systemic vascular dysfunction, and epigenetic changes. The specific molecular mechanisms of PM 2.5-induced cardiotoxicity effects are still under active investigation. We hypothesized that PM 2.5 exposure may induce different effects in different life phases, such as juvenile, adult, and older subpopulations. However, the susceptibility of individuals of different ages to cardiovascular disease caused by PM 2.5 exposure has not been investigated.
Furthermore, exposure to diesel exhaust or PM 2.5 during early life can cause significant cardiovascular dysfunction in adulthood. Recent studies have demonstrated that exposure to PM 2.5 promotes systolic and diastolic dysfunction, and exposure to carbon black impairs cardiac function in senescent mice. Several studies have suggested that susceptible individuals are at greater risk for PM 2.5-associated cardiovascular morbidity and mortality including the elderly, women, and patients with preexisting coronary artery disease and diabetes. Furthermore, PM 2.5 does not affect all people equally. It has been reported that seasonal variation in the association between PM 2.5 and cardiovascular hospitalization. Even in the same region, PM 2.5 from different seasons appears to have different chemical composition. However, the physicochemical properties of ambient PM 2.5 in different regions varies because of a number of factors including local geography, proximity to emission sources, and meteorology. Epidemiological evidence supports a robust association between exposure to PM 2.5 and cardiovascular diseases morbidity and mortality, such as myocardial infarction, heart failure, heart attacks, stroke, heart rhythm disturbances, and sudden death. The mechanism by which PM 2.5 exposure resulted in cardiac lesions might involve oxidative stress, NADPH oxidase, TGFβ1, and Smad-dependent pathways.Īir pollution, mostly by fine particulate matter (PM 2.5), leads to 3.3 million premature deaths per year worldwide, predominantly in Asia. 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. Juvenile and older mice are more sensitive to PM 2.5 than adults and suffer from cardiac dysfunction. 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. 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. 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. 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. ROS generation was detected by photocatalysis using 2′,7′-dichlorodihydrofluorescein diacetate (DCFHDA). Left ventricles were processed for histology to assess myocardial fibrosis.
Cardiac function was assessed by echocardiography. Heart rate and systolic blood pressure were measured using a tail-cuff system. 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. Methodsįemale 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. 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. Cardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function.