Cardiovascular Remodeling in Response to Long-Term Exposure to Fine Particulate Matter Air Pollution

Abstract

Background Air pollution is a pervasive environmental health hazard that occurs over a lifetime of exposure in individuals from many industrialized societies. However, studies have focused primarily on exposure durations that correspond to only a portion of the lifespan. We therefore tested the hypothesis that exposure over a considerable portion of the lifespan would induce maladaptive cardiovascular responses. Methods and Results C57BL/6 male mice were exposed to concentrated ambient particles <2.5 μm (particulate matter, PM or PM2.5) or filtered air (FA), 6 h/d, 5 d/wk, for 9 months. Assessment of cardiac contractile function, coronary arterial flow reserve, isolated cardiomyocyte function, expression of hypertrophic markers, calcium handling proteins, and cardiac fibrosis were then performed. Mean daily concentrations of PM2.5 in the exposure chamber versus ambient daily PM2.5 concentration at the study site were 85.3 versus 10.6 μg/m3 (7.8-fold concentration), respectively. PM2.5 exposure resulted in increased hypertrophic markers leading to adverse ventricular remodeling characterized by myosin heavy chain (MHC) isoform switch and fibrosis, decreased fractional shortening (39.8±1.4 FA versus 27.9±1.3 PM, FS%), and mitral inflow patterns consistent with diastolic dysfunction (1.95±0.05 FA versus 1.52±0.07 PM, E/A ratio). Contractile reserve to dobutamine was depressed (62.3±0.9 FA versus 49.2±1.5 PM, FS%) in response to PM2.5 without significant alterations in maximal vasodilator flow reserve. In vitro cardiomyocyte function revealed depressed peak shortening (8.7±0.6 FA versus 7.0±0.4 PM, %PS) and increased time-to-90% shortening (72.5±3.2 FA versus 82.8±3.2 PM, ms) and relengthening (253.1±7.9 FA versus 282.8±9.3 PM, ms), which were associated with upregulation of profibrotic markers and decreased total antioxidant capacity. Whole-heart SERCA2a levels and the ratio of α/β-MHC were both significantly decreased (P<0.05) in PM2.5-exposed animals, suggesting a switch to fetal programming. Conclusions Long-term exposure to environmentally relevant concentrations of PM2.5 resulted in a cardiac phenotype consistent with incipient heart failure.

Early life exposure to air pollution induces adult cardiac dysfunction

“…Pregnancy was confirmed and time-dated with the presence of a vaginal plug. Dams were exposed to concentrated PM2.5 from the Columbus, OH region using the OASIS-1 aerosol concentration system, which has been previously described (47). Dams were placed into the exposure system for 6 h a day, 7 days a wk, separated into either PM 2.5 exposure or air that has been filtered by a high-efficiency air filter (FA).…”

“…Cardiomyocytes were isolated as previously described (33,42,43,46,47). Briefly, hearts were removed and retrogradely perfused through the aorta with Liberase and trypsin until digested.…”

“…Isolated cells were then plated on laminin-coated glassbottom inserts (Cell MicroControls, Norfolk, VA) for functional analyses. Glass-bottom inserts were perfused with warm contractile buffer (27,33,42,43,46,47) within a flow chamber attached to an Olympus IX-71 microscope. Cells were stimulated (1 Hz, 3-ms duration) with a Myopacer Field-Stimulator system (IonOptix, Milton, MA), and functional properties of the cells were evaluated with the Sarclen Sarcomere Length Acquisition Module using the Myocam-S Digital CCD camera video imaging system (IonOptix).…”

Ambient and household air pollution: complex triggers of disease

“…Our laboratory (84) demonstrated that mice exposed to concentrated PM 2.5 over a period of 9 mo demonstrated decreased cardiac function. Male mice that were exposed to PM 2.5 showed higher rates of cardiac remodeling characterized by increases in both left ventricular end-systolic and enddiastolic diameters compared with filtered air-exposed control mice.…”

Air pollution and cardiovascular hospital admissions in Kerman, Iran

“…Several studies conducted in Europe and America have shown that air pollution is associated with cardiovascular and respiratory deaths and hospital admissions. Although more studies have focused on the respiratory system as the main target of air pollution adverse effects, but recent evidence has shown that air pollution can also affect the cardiovascular system and particularly lead to ischemic heart diseases [12][13][14] . The harmful effects of increasing concentrations of particulate matter (PM) and carbon monoxide and other pollutants has been demonstrated as an increase in hospital emergency admissions for respiratory diseases in several studies [15] .…”