Title: Ambient air particulate matter exposure and tissue factor expression in atherosclerosis.
Authors: Sun, Qinghua; Yue, Peibin; Kirk, Rita I; Wang, Aixia; Moatti, Didier; Jin, Ximei; Lu, Bo; Schecter, Alison D; Lippmann, Morton; Gordon, Terry; Chen, Lung Chi; Rajagopalan, Sanjay
Published In Inhal Toxicol, (2008 Jan)
Abstract: Recent studies have suggested a link between inhaled particulate matter (PM) exposure and atherogenesis. We investigated tissue factor (TF) expression with ambient fine particulate matter (diameter < 2.5 microm, PM(2.5)) exposure and in response to in vitro exposure to fine and ultrafine PM in cultured human bronchial epithelial cells, vascular smooth muscle cells (hSMCs), and monocytes. ApoE-/- mice, fed with normal chow (NC) or high-fat chow (HFC), were exposed to concentrated PM(2.5) or filtered air (FA) for 6 mo (6 h/day, 5 day/wk, n = 28). Following in vivo ultrasound bio-microscopy (UBM) assessment of plaque area, macrophage infiltration (CD68) and TF expression in the aorta were quantified. Cultured cells were incubated with size-fractionated PM from cascade impactors, or with standard reference PM material (SRM, number 1649a) and assayed for TF protein, mRNA, and activity. UBM-derived plaque areas were 7 +/- 1% larger in the PM(2.5)-HFC than the FA-HFC group (p = .04), but not significantly different between the PM(2.5)-NC and FA-NC groups (p = .07). Immunohistochemistry revealed increased TF (15 +/- 3% vs. 8 +/- 2%, p < .01) and macrophage infiltration (19 +/- 2% vs. 14 +/- 3%, p < .01) in the plaques of PM(2.5)-HFC compared with FA-HFC groups. Impactor-collected PM(2.5) and ultrafine particles consistently increased TF protein in bronchial epithelial cells, monocytes, and hSMCs. TF mRNA expression increased rapidly (within 1 h) in response to SRM PM. We conclude that in vivo and in vitro exposure to ambient air PM(2.5) induces TF expression.
PubMed ID: 18236227
MeSH Terms: Air Pollution/adverse effects*; Animals; Apolipoproteins E/deficiency; Apolipoproteins E/genetics; Atherosclerosis/diagnostic imaging; Atherosclerosis/etiology; Atherosclerosis/metabolism*; Bronchi/drug effects; Bronchi/metabolism; Bronchi/pathology; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Environmental Exposure/adverse effects*; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Epithelial Cells/pathology; Gene Expression Regulation/drug effects; Gene Silencing; Humans; Image Processing, Computer-Assisted; Inhalation Exposure; Male; Mice; Mice, Knockout; Monocytes/drug effects; Monocytes/metabolism; Monocytes/pathology; Muscle, Smooth, Vascular/drug effects; Muscle, Smooth, Vascular/metabolism; Muscle, Smooth, Vascular/pathology; Particulate Matter/adverse effects*; RNA, Messenger/metabolism; Thromboplastin/genetics; Thromboplastin/metabolism*; Ultrasonography