CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.
CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.
Authors: Loren E Wold; Zhekang Ying; Kirk R Hutchinson; Markus Velten; Matthew W Gorr; Christina Velten; Dane J Youtz; Aixia Wang; Pamela A Lucchesi; Qinghua Sun; Sanjay Rajagopalan Journal: Circ Heart Fail Date: 2012-06-01 Impact factor: 8.790
Authors: Thomas Kampfrath; Andrei Maiseyeu; Zhekang Ying; Zubair Shah; Jeffrey A Deiuliis; Xiaohua Xu; Nisharahmed Kherada; Robert D Brook; Kongara M Reddy; Nitin P Padture; Sampath Parthasarathy; Lung Chi Chen; Susan Moffatt-Bruce; Qinghua Sun; Henning Morawietz; Sanjay Rajagopalan Journal: Circ Res Date: 2011-01-27 Impact factor: 17.367
Authors: Amie K Lund; JoAnn Lucero; Melissa Harman; Michael C Madden; Jacob D McDonald; Jean Clare Seagrave; Matthew J Campen Journal: Am J Respir Crit Care Med Date: 2011-04-14 Impact factor: 21.405
Authors: Hui-Hui Tan; M Isabel Fiel; Qinghua Sun; Jinsheng Guo; Ronald E Gordon; Lung-Chi Chen; Scott L Friedman; Joseph A Odin; Jorge Allina Journal: J Immunotoxicol Date: 2009-12 Impact factor: 3.000
Authors: Jesus A Araujo; Berenice Barajas; Michael Kleinman; Xuping Wang; Brian J Bennett; Ke Wei Gong; Mohamad Navab; Jack Harkema; Constantinos Sioutas; Aldons J Lusis; Andre E Nel Journal: Circ Res Date: 2008-01-17 Impact factor: 17.367