Effect of ambient particulate matter exposure on hemostasis

Cozzi, Emily; Wingard, Christopher J.; Cascio, Wayne E.; Devlin, Robert B.; Miles, Jeremy J.; Bofferding, April; Lust, Robert M.; Scott, Michael R. Van; Henriksen, Ruth Ann

doi:10.1016/j.trsl.2006.12.009

Cited by 57 publications

(40 citation statements)

References 70 publications

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“…54 Several studies have demonstrated an association between PM exposure and plasma PAI-1 levels in humans and in mice. 51,55 In this study, we detected only a slight increase of circulating PAI-1 but a 3-fold increase of the lung PAI-1 level after PM 2.5 exposure, indicating that the dose of PM 2.5 exposure (100 g/mouse) used in our studies is not sufficient to trigger systemic coagulation responses, but potent enough to induce localized lung pathologic changes. Although there was no significant difference in plasma PAI-1 levels between Sirt1 Ϫ/Ϫ and Sirt1 ϩ/ϩ littermates, lung PAI-1 level was higher in Sirt1 Ϫ/Ϫ mice after PM 2.5 treatment, indicating that Sirt1 deletion may lead to abnormal lung PAI-1 expression.…”

Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 50%

“…15 It has been demonstrated that short-term PM exposure significantly decreased plasma TFPI level. 51 Decreased circulating TFPI levels have been linked to venous thrombosis 52 ; however, lung TFPI expression and regulation by Sirt1 after PM exposure have not been investigated. In this study, we demonstrated that lung TFPI expression was decreased after PM exposure, and Sirt1 deletion resulted in further reduction of TFPI levels in the lung, suggesting that Sirt1 could control coagulation responses by regulating TFPI expression.…”

Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 99%

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Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Liu

Liang

et al. 2012

Blood

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Exposure to ambient particulate matter (PM) air pollution has been reported to trigger inflammation and thrombosis. However, molecular mechanisms underlying the modulation of coagulation pathways in PM-induced thrombosis remain largely unknown. We report here that Sirt1, a member of class III histone deacetylase, controls lung inflammation and coagulation after PM exposure. Sirt1 knock-out mice exhibited aggravated lung vascular leakage and inflammation after PM exposure, which was correlated with increased NF-B acetylation and activation. Furthermore, Sirt1 knock-out mice were highly susceptible to PM-induced lung coagulation as demonstrated by increased fibrin formation. The increased fibrin formation was associated with reduced tissue factor pathway inhibitor (TFPI) expression and increased plasminogen activator inhibitor-1 (PAI-1) activity in the lungs, thus favoring elevated coagulation and disrupted fibrinolysis responses. Thrombomodulin (TM), a central player of the anticoagulant protein C system, is regulated by Kruppel-like factor 2 (KLF2) at the transcriptional level. IntroductionExposure to ambient particulate matter (PM) air pollution has been associated with impaired pulmonary function and increased cardiovascular disease-related mortality including inflammation and thrombosis. 1-5 Acute exposure to increased ambient fine particulate matter Ͻ 2.5 m in diameter (PM 2.5 ) was estimated to cause the premature deaths of tens of thousands of people each year in the United States. 6 Urban particulate matter (UPM) PM 2.5, one of the major air pollutants closely monitored by the US Environmental Protection Agency (EPA), is a complex mixture of substances that are directly emitted into the air from dust, soot, smoke, and combustion. 6 To protect public health, the EPA issued the current 24-hour PM 2.5 standard at 35 g/m 3 . 6 Despite the enormous health problems caused by PM 2.5 exposure, there have been few studies performed to explore the molecular mechanisms of PM 2.5 -induced lung vascular dysfunction. PM 2.5 can reach deep in the lung to the small airway and alveoli, 6 and directly cause lung inflammation and injury. [7][8][9][10][11][12][13] The pulmonary complications may lead to detrimental effects on other organs, particularly cardiovascular dysfunction such as systemic microvascular dysfunction and thrombosis. 1,2,4,5,13 A recent study demonstrated that short-term UPM exposure triggered the activation of primary hemostasis in healthy mice, with no substantial secondary hemostasis activation, leading to arterial but not venous thrombosis. 5 Whereas another study showed that short-term UPM exposure may cause activation of coagulation responses and fibrin formation in the lung. 14 Tissue factor pathway inhibitor (TFPI) and plasminogen activator inhibitor-1 (PAI-1) play important roles in coagulation and fibrinolysis cascades, respectively. TFPI is an inhibitor of tissue factor (TF)-mediated coagulation responses. 15 PAI-1, on the other hand, is a major regulator of fibrinolysis, which functions by in...

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Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 50%

Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 99%

Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Liu

Liang

et al. 2012

Blood

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“…341 Other findings also support potential procoagulant and thrombotic effects of PM. 342,343 These collective studies suggest that both short-and longterm PM inhalation can enhance thrombotic and coagulation tendencies, potentially via increases in circulating histamine and inflammatory cytokines and/or activated white cells and platelets. The plausibility of these pathways is supported by the well-recognized cross talk between inflammation and thrombosis.…”

Section: Thrombosis and Coagulationmentioning

confidence: 99%

Particulate Matter Air Pollution and Cardiovascular Disease

Brook¹,

Rajagopalan²,

Pope³

et al. 2010

Circulation

5,431

3,225

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Abstract-In 2004, the first American Heart Association scientific statement on "Air Pollution and Cardiovascular Disease" concluded that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality. In the interim, numerous studies have expanded our understanding of this association and further elucidated the physiological and molecular mechanisms involved. The main objective of this updated American Heart Association scientific statement is to provide a comprehensive review of the new evidence linking PM exposure with cardiovascular disease, with a specific focus on highlighting the clinical implications for researchers and healthcare providers. The writing group also sought to provide expert consensus opinions on many aspects of the current state of science and updated suggestions for areas of future research. On the basis of the findings of this review, several new conclusions were reached, including the following: Exposure to PM Ͻ2.5 m in diameter (PM 2.5 ) over a few hours to weeks can trigger cardiovascular disease-related mortality and nonfatal events; longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within more highly exposed segments of the population by several months to a few years; reductions in PM levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM 2.5 exposure and cardiovascular morbidity and mortality. This body of evidence has grown and been strengthened substantially since the first American Heart Association scientific statement was published. Finally, PM 2.5 exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality. (Circulation. 2010;121:2331-2378.)

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“…Likewise, exposure of rats to concentrated PM from New York City air did not alter levels of fibrinogen, FVII or thrombin-antithrombin complexes (TAT) (Nadziejko et al 2002). Significant increases in the level of fibrinogen, or decreases in the levels of the anticoagulant proteins activated protein C or tissue factor pathway inhibitor (TFPI) upon short-term PM exposure have been observed in rodents, but at doses of 100 μg or higher per mouse (Cozzi et al 2007, Inoue et al 2006. One study stands out among other studies on procoagulant changes and PM exposure: Mutlu et al observed a pronounced prothrombotic phenotype in mice upon a single intratracheal instillation of as few as 10 μg of PM 10 , characterized by shortenings in bleeding time, PT and aPTT, and relatively high increases in the levels of circulating blood platelets, FVII, FVIII, FX and fibrinogen (Mutlu et al 2007).…”

Section: Pathophysiologymentioning

confidence: 99%

“…While studies, based on controlled exposure to diluted diesel exhaust , Carlsten et al 2007 or concentrated ambient particles (Ghio et al 2003), did not observe increases in the levels of plasminogen activator inhibitor-1 (PAI-1), some epidemiological or animal studies, focussing on urban PM, did: a study in 76 young healthy students demonstrated elevated PAI-1 concentrations in association with the mean PM 2.5 or PM 10 concentration at their university's campus over 1 to 3 days (Chuang et al 2007). Likewise, urban PM upregulated PAI-1 levels, 24 hours after intratracheal instillation in mice (Cozzi et al 2007). PM exposure could also impair the endothelial repair mechanisms by reducing the number of endothelial progenitor cells, as demonstrated by a recent report (O'Toole et al 2010).…”

Section: Endothelial Function and Fibrinolysismentioning

confidence: 99%