Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution

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.

Long-term exposure to environmentally relevant concentrations of PM(2.5) resulted in a cardiac phenotype consistent with incipient heart failure.

C57BL/6 male mice were exposed to concentrated ambient particles <2.5 µm (particulate matter, PM or PM(2.5)) 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 PM(2.5) in the exposure chamber versus ambient daily PM(2.5) concentration at the study site were 85.3 versus 10.6 µg/m(3) (7.8-fold concentration), respectively. PM(2.5) 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 PM(2.5) 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 re-lengthening (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 PM(2.5)-exposed animals, suggesting a switch to fetal programming. Conclusions: Long-term exposure to environmentally relevant concentrations of PM(2.5) resulted in a cardiac phenotype consistent with incipient heart failure.