Atmospheric ultrafine particles promote vascular calcification via the NF-κB signaling pathway

Li R, Mittelstein D, Kam W, Pakbin P, Du Y, Tintut Y, Navab M, Sioutas C, Hsiai T. Atmospheric ultrafine particles promote vascular calcification via the NF-kappa B signaling pathway. Am J Physiol Cell Physiol 304: C362-C369, 2013. First published December 12, 2012; doi:10.1152/ajpcell.00322.2012.-Exposure to atmospheric fine particulate matter (PM2.5) is a modifiable risk factor of cardiovascular disease. Ultrafine particles (UFP, diameter <0.1 mu m), a subfraction of PM2.5, promote vascular oxidative stress and inflammatory responses. Epidemiologic studies suggest that PM exposure promotes vascular calcification. Here, we assessed whether UFP exposure promotes vascular calcification via NF-kappa B signaling. UFP exposure at 50 mu g/ml increased alkaline phosphatase (ALP) activity by 4.4 +/- 0.2-fold on day 3 (n = 3, P < 0.001) and matrix calcification by 3.5 +/- 1.7-fold on day 10 (n = 4, P < 0.05) in calcifying vascular cells (CVC), a subpopulation of vascular smooth muscle cells with osteoblastic potential. Treatment of CVC with conditioned media derived from UFP-treated macrophages (UFP-CM) also led to an increase in ALP activities and matrix calcification. Furthermore, both UFP and UFP-CM significantly increased NF-kappa B activity, and cotreatment with an NF-kappa B inhibitor, JSH23, attenuated both UFP- and UFP-CM-induced ALP activity and calcification. When low-density lipoprotein receptor-null mice were exposed to UFP at 359.5 mu g/m(3) for 10 wk, NF-kappa B activation and vascular calcification were detected in the regions of aortic roots compared with control filtered air-exposed mice. These findings suggest that UFP promotes vascular calcification via activating NF-kappa B signaling.