The Oxidized Low-Density Lipoprotein Receptor Mediates Vascular Effects of Inhaled Vehicle Emissions

Lund, Amie K.; Lucero, JoAnn; Harman, Melissa; Madden, Michael C.; McDonald, Jacob D.; Seagrave, Jean Clare; Campen, Matthew J.

doi:10.1164/rccm.201012-1967oc

Cited by 91 publications

(90 citation statements)

References 40 publications

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“…Em muitos países, as doenças cardiovasculares são responsáveis pela maior sobrecarga de doença, e a sua associação com fatores ambientais, particularmente com a poluição do ar, está bem documentada 1 , embora os mecanismos subjacentes ainda precisem ser determinados. Consistente com alguns achados anteriores, um estudo experimental recente demonstrou pela primeira vez que a exposição respiratória ao material particulado estimula o processo de aterogenêse 2 ; portanto, esse pode ser o elo entre poluição do ar e doenças cardiovasculares. Além disso, sugere-se que o estado pró-inflamatório contribui para a ocorrência de fatores de risco cardiometabólicos, e a associação da poluição atmosférica com esses fatores de risco está documentada tanto em adultos 3 quanto em adolescentes 4 .…”

Section: Introductionunclassified

Association of air pollution and hematologic parameters in children and adolescents

Poursafa¹,

Kelishadi²,

Amini³

et al. 2011

J Pediatr (Rio J)

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Objective: To assess the relationship of air pollution and hematologic parameters in a population-based sample of children and adolescents. Methods:This cross-sectional study was conducted in 2009-2010 among school students randomly selected from different areas of Isfahan city, the second largest and most air-polluted city in Iran. The association of air pollutants levels with hemoglobin, platelets, red and white blood cells (RBC and WBC, respectively) levels was determined by multiple linear and logistic regression analyses, after adjustment for age, gender, anthropometric measures, meteorological factors, and dietary and physical activity habits. Results:The study participants consisted of 134 students (48.5% boys) with a mean age of 13.10±2.21 years. While the mean Pollutant Standards Index (PSI) was at moderate level, the mean particulate matter ≤ 10 µm (PM 10 ) was more than twice the normal level. Multiple linear regression analysis showed that PSI and most air pollutants, notably PM 10 , had significant negative relationship with hemoglobin and RBC count, and positive significant relationship with WBC and platelet counts. The odds ratio of elevated WBC increased as the quartiles of PM 10 , ozone and PSI increased, however these associations reached to significant level only in the highest quartile of PM 10 and PSI. The corresponding figures for hemoglobin and RBC were in opposite direction. Conclusions:The association of air pollutants with hematologic parameters and a possible pro-inflammatory state is highlighted. The presence of these associations with PM 10 in a moderate mean PSI level underscores the necessity to re-examine environmental health policies for the pediatric age group.J Pediatr (Rio J). 2011;87(4): Air pollution, cell blood count, atherosclerosis, inflammation, children, prevention. ResumoObjetivo: Avaliar a relação entre poluição atmosférica e parâ-metros hematológicos em uma amostra populacional de crianças e adolescentes. Métodos:Este estudo transversal foi realizado em 2009-2010 com estudantes escolhidos aleatoriamente de diversas áreas de Isfahan, a segunda maior e mais poluída cidade iraniana. A associação entre os níveis de poluentes do ar e os de hemoglobina, plaquetas, glóbulos brancos (GB) e glóbulos vermelhos (GV) foi determinada pelas análises linear múltipla e de regressão logística ajustadas para idade, sexo, medidas antropométricas, fatores meteorológicos, e hábitos alimentares e de atividade física. Resultados:Participaram do estudo 134 estudantes (48,5% meninos), com idade média de 13,10±2,21 anos. Com níveis moderados de Pollutant Standards Index (PSI), a média de material particulado (particulate matter) ≤ 10 µm (PM 10 ) foi mais do que o dobro do normal. A análise de regressão linear demonstrou que o PSI e a maioria dos poluentes atmosféricos, especialmente PM 10 , estiveram negativamente relacionados com a contagem de hemoglobina e GV e positivamente relacionados com a contagem de GB e plaquetas. O odds ratio de uma elevação nos GB aumentou conforme os quart...

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Section: Introductionunclassified

Association of air pollution and hematologic parameters in children and adolescents

Poursafa¹,

Kelishadi²,

Amini³

et al. 2011

J Pediatr (Rio J)

View full text Add to dashboard Cite

show abstract

“…Chronically, diesel exhaust exposure leads to progression of atherosclerotic lesions, both in terms of size and complexity (Campen, Lund et al 2010, Bai, Kido et al 2011, Miller, McLean et al 2013). A key facet of diesel exposure is the vascular influx of macrophages, which can be seen as early as a week of exposures (Lund, Lucero et al 2011). Studies suggested that this inflammatory response to diesel was mediated via the LOX-1 receptor, suggesting that blood components interacting with endothelial cells and potentially circulating leukocytes may be central to such effects (Lund, Lucero et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…A key facet of diesel exposure is the vascular influx of macrophages, which can be seen as early as a week of exposures (Lund, Lucero et al 2011). Studies suggested that this inflammatory response to diesel was mediated via the LOX-1 receptor, suggesting that blood components interacting with endothelial cells and potentially circulating leukocytes may be central to such effects (Lund, Lucero et al 2011). Importantly, such studies collectively implicate inflammatory activation of endothelial cells as a crucial intermediate process that drives both acute and chronic disease.…”

Section: Discussionmentioning

confidence: 99%

“…Probing the transcriptional responses provides clues as to what the compositionally altered plasma may activate in endothelial cells, but whether such changes are sufficient to impact homeostasis remains unclear. Based on recent findings of roles for multiligand receptors LOX-1 (Lund, Lucero et al 2011), TLR4 (Kampfrath, Maiseyeu et al 2011), and CD36 (Robertson, Colombo et al 2013, Rao, Zhong et al 2014), all of which could generate a portion of the inflammatory signaling responses observed in the plasma-treated endothelial cells (Silverstein and Febbraio 2009, Sikorski, Czerwoniec et al 2011, Pirillo, Norata et al 2013), ligands to such receptors are a likely intermediate that could be assessed in future research.…”

Section: Discussionmentioning

confidence: 99%

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Endothelial inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions

Schisler

Ronnebaum

Madden

et al. 2015

Inhalation Toxicology

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Background Air pollution, especially emissions derived from traffic sources, is associated with adverse cardiovascular outcomes. However, it remains unclear how inhaled factors drive extrapulmonary pathology. Objectives Previously, we found that canonical inflammatory response transcripts were elevated in cultured endothelial cells treated with plasma obtained after exposure compared with pre-exposure samples or filtered air (sham) exposures. While the findings confirmed the presence of bioactive factor(s) in the plasma after diesel inhalation, we wanted to better examine the complete genomic response to investigate 1) major responsive transcripts and 2) collected response pathways and ontogeny that may help to refine this method and inform the pathogenesis. Methods We assayed endothelial RNA with gene expression microarrays, examining the responses of cultured endothelial cells to plasma obtained from 6 healthy human subjects exposed to 100 μg/m3 diesel exhaust or filtered air for 2 h on separate occasions. In addition to pre-exposure baseline samples, we investigated samples obtained immediately-post and 24h-post exposure. Results Microarray analysis of the coronary artery endothelial cells challenged with plasma identified 855 probes that changed over time following diesel exhaust exposure. Over-representation analysis identified inflammatory cytokine pathways were upregulated both at the 2 and 24 h condition. Novel pathways related to FOX transcription factors and secreted extracellular factors were also identified in the microarray analysis. Conclusions These outcomes are consistent with our recent findings that plasma contains bioactive and inflammatory factors following pollutant inhalation. The specific study design implicates a novel pathway related to inflammatory blood borne components that may drive the extrapulmonary toxicity of ambient air pollutants.

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“…DE exposure alone did not increase plasma TBARS. However, exposure of ApoE -/-mice to MVE did result in enhanced plasma TBARS (Lund et al 2011 ), suggesting a greater toxicity for MVE in comparison to DE alone. We have recently shown that ApoE -/-mice exposed to DE for 2 weeks led to increased plasma levels of 8-isoprostanes, 12-HETEs and 13-HODEs, oxidized products of arachidonic and linoleic acid, respectively (Yin et al 2013 ).…”

Section: Effects On Lipids: a Potential Missing Linkmentioning

confidence: 94%

Air Pollution, Lipids and Atherosclerosis

Araujo

Rosenfeld

2015

Molecular and Integrative Toxicology

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The Oxidized Low-Density Lipoprotein Receptor Mediates Vascular Effects of Inhaled Vehicle Emissions

Cited by 91 publications

References 40 publications

Association of air pollution and hematologic parameters in children and adolescents

Association of air pollution and hematologic parameters in children and adolescents

Endothelial inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions

Air Pollution, Lipids and Atherosclerosis

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