Early life exposure to air pollution induces adult cardiac dysfunction

Abstract

Exposure to ambient air pollution contributes to the progression of cardiovascular disease, particularly in susceptible populations. The objective of the present study was to determine whether early life exposure to air pollution causes persistent cardiovascular consequences measured at adulthood. Pregnant FVB mice were exposed to filtered (FA) or concentrated ambient particulate matter (PM2.5) during gestation and nursing. Mice were exposed to PM2.5 at an average concentration of 51.69 μg/m3 from the Columbus, OH region for 6 h/day, 7 days/wk in utero until weaning at 3 wk of age. Birth weight was reduced in PM2.5 pups compared with FA (1.36 ± 0.12 g FA, n = 42 mice; 1.30 ± 0.15 g PM2.5, n = 67 P = 0.012). At adulthood, mice exposed to perinatal PM2.5 had reduced left ventricular fractional shortening compared with FA-exposed mice (43.6 ± 2.1% FA, 33.2 ± 1.6% PM2.5, P = 0.001) with greater left ventricular end systolic diameter. Pressure-volume loops showed reduced ejection fraction (79.1 ± 3.5% FA, 35.5 ± 9.5% PM2.5, P = 0.005), increased end-systolic volume (10.4 ± 2.5 μl FA, 39.5 ± 3.8 μl PM2.5, P = 0.001), and reduced dP/d t maximum (11,605 ± 200 μl/s FA, 9,569 ± 800 μl/s PM2.5, P = 0.05) and minimum (−9,203 ± 235 μl/s FA, −7,045 ± 189 μl/s PM2.5, P = 0.0005) in PM2.5-exposed mice. Isolated cardiomyocytes from the hearts of PM2.5-exposed mice had reduced peak shortening (%PS, 8.53 ± 2.82% FA, 6.82 ± 2.04% PM2.5, P = 0.003), slower calcium reuptake (τ, 0.22 ± 0.09 s FA, 0.26 ± 0.07 s PM2.5, P = 0.048), and reduced response to β-adrenergic stimulation compared with cardiomyocytes isolated from mice that were exposed to FA. Histological analyses revealed greater picro-sirius red-positive-stained areas in the PM2.5 vs. FA group, indicative of increased collagen deposition. We concluded that these data demonstrate the detrimental role of early life exposure to ambient particulate air pollution in programming of adult cardiovascular diseases and the potential for PM2.5 to induce persistent cardiac dysfunction at adulthood.

PM 2.5 exposure in utero contributes to neonatal cardiac dysfunction in mice

“…However, at 14 days of age pups that were born to PM 2.5 exposed dams had significantly higher body weights compared to pups born to FA exposed dams. This observation is in agreement with our previous work where we demonstrated that mice exposed during the combined in utero and perinatal periods to PM 2.5 were born with LBW, but had significantly higher body weights at adulthood 9 . Similarly, it has also been shown that infants exposed to traffic-related pollution during early life gained postnatal weight despite reduced fetal growth 7 .…”

“…An understanding of developmental plasticity provides a conceptual basis for these observations 8 . There is also substantial evidence suggesting a positive correlation between particulate air pollution exposure and adverse cardiovascular outcomes during the postnatal periods 9, 10 . In another study, cardiomyocytes cultured in media from PM-treated lung epithelial cells demonstrated contractile dysfunction 11 .…”

Environmental factors in cardiovascular disease

“…80 Air-pollution exposure during pregnancy is also associated with alterations in blood pressure 81 and birth weight, 80 as well as with the occurrence of preterm delivery, 82 and with future risk of CVD. 83 In conjunction with haemodynamic effects, inhaled particulate matter negatively affects vascular function. Minor increases in residential PM 2.5 levels have been associated with clinically relevant reductions in endothelial function (measured as a decrease from baseline in flow-mediated dilatation) among individuals in large US cohort studies.…”

A perspective on the developmental toxicity of inhaled nanoparticles

“…A similar exposure applied only throughout pregnancy affected only young adult male mice, exhibiting increased body weight, reduced blood pressure without change in basal cardiac function, and a higher susceptibility to heart failure than controls [99]. More recently, it was shown in mice that daily exposure during gestation and until weaning to ambient air particles at a concentration of 51.69 g/m 3 , 6 h/day, 7 days a week induced persistent cardiac dysfunction in the adult offspring [146].…”