Abstract 1385: Atmospheric Nanoparticles Induce Vascular Oxidative Stress via JNK Activation
Epidemiological studies have closely linked the exposure of particulate air pollution with an increased incidence of cardiovascular diseases. Smaller particles pose a higher risk. Ambient ultra fine particles (UFP) from diesel vehicle engines with a diameter less than 180 nm are pro-atherogenic in apoE knockout mice and may constitute a major cardiovascular risk in human. We posited that circulating UFP induced vascular oxidative stress via JNK activation in human aortic endothelial cells (HAEC). To test this, we collected the diesel nanoparticles from a 1998 Kenworth truck running at idle condition without any emission control technology, using a high volume sampler. The mode diameter of the collected nanoparticles in this study was less than 50 nm. Our data indicated that UFP induced superoxide production (O2.-) in a dose dependent manner (control: 0.051±0.015; 12.5 μg/ml UFP: 0.21±0.02; 25 μg/ml UFP: 0.44±0.03; 50 μg/ml UFP: 0.71±0.07; n=3, P <0.0005, 0.001 and 0.005, respectively) as measured by NBT assay. UFP (50μg/ml) also increased mitochondrial O2.- generation by 1.91±0.07 fold ( n=3, p<0.009) by flow cytometry (FACS) analysis of MitoSOX red and induced mRNA expression of hemeoxygenase-1 (HO-1) by 17.3 ± 2.8 fold (n=3, P<0.015) and tissue factor (TF) by 8.9 ± 0.2 fold (n=3, P<0.0002). JNK was phosphorylated by UFP and JNK inhibitor SP600125 significantly inhibited UFP (25μg/ml)-induced O2.- production by 58% (n=3, p<0.03), UFP(50μg/ml)-stimulated HO-1 mRNA by 62% and TF RNA by 63%(n=3, P<0.03). Our data suggest that UFP induced vascular oxidative stress in HAEC via a JNK-dependent signal pathway in HAEC, thus providing a basis for further study of the mechanisms of atmospheric nanoparticles on atherosclerosis.