title: Atmospheric ultrafine particles promote vascular calcification via the NF-κB signaling pathway.
abstract: Exposure to atmospheric fine particulate matter (PM(2.5)) is a modifiable risk factor of cardiovascular disease. Ultrafine particles (UFP, diameter <0.1 μm), a subfraction of PM(2.5), 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-κB signaling. UFP exposure at 50 μg/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-κB activity, and cotreatment with an NF-κB 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 μg/m(3) for 10 wk, NF-κB 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-κB signaling.
authors.affiliation: Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Rongsong
authors.initials: R
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Mittelstein
authors.forename: Winnie
authors.initials: W
authors.lastname: Kam
authors.forename: Payam
authors.initials: P
authors.lastname: Pakbin
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Du
authors.forename: Yin
authors.initials: Y
authors.lastname: Tintut
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Tzung
authors.initials: T
authors.lastname: Hsiai
mesh_terms: D000469:Alkaline Phosphatase; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010316:Particle Size; D052638:Particulate Matter / Q000494:pharmacology / Q000633:toxicity*; D015398:Signal Transduction; D061205:Vascular Calcification / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; D016328:NF-kappa B; D052638:Particulate Matter; D000469:Alkaline Phosphatase