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Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability--the VA Normative Aging Study.

ABSTRACT: Many studies have shown that exposures to air pollution are associated with cardiovascular events, although the mechanism remains to be clarified. To identify whether exposures to ambient particles act on autonomic function via the lipid/endothelial metabolism pathway, whether effects of particulate matter <2.5 mum in aerodynamic diameter (PM(2.5)) on heart rate variability (HRV) were modified by gene polymorphisms related to those pathways were evaluated.HRV and gene data from the Normative Aging Study and PM(2.5) from a monitor located a kilometre from the examination site were used. A mixed model was fitted to investigate the associations between PM(2.5) and repeated measurements of HRV by gene polymorphisms of apolipoprotein E (APOE), lipoprotein lipase (LPL) and vascular endothelial growth factor (VEGF) adjusting for potential confounders chosen a priori.A 10 microg/m(3) increase in PM(2.5) in the 2 days before the examination was associated with 3.8% (95% CI 0.2% to 7.4%), 7.8% (95 CI 0.4% to 15.3%) and 10.6% (95% CI 1.8% to 19.4%) decreases of the standard deviation of normal-to-normal intervals, the low frequency and the high frequency, respectively. Overall, carriers of wild-type APOE, LPL and VEGF genes had stronger effects of particles on HRV than those with hetero- or homozygous types. Variations of LPL-N291S, LPL-D9N and APOE-G113C significantly modified effects of PM(2.5) on HRV.Associations between PM(2.5) and HRV were modified by gene polymorphisms of APOE, LPL and VEGF; the biological metabolism remains to be identified.

SUBMITTER: Ren C

PROVIDER: S-EPMC3935361 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability--the VA Normative Aging Study.

Ren C C Baccarelli A A Wilker E E Suh H H Sparrow D D Vokonas P P Wright R R Schwartz J J

Journal of epidemiology and community health 20100101 1

<h4>Background</h4>Many studies have shown that exposures to air pollution are associated with cardiovascular events, although the mechanism remains to be clarified. To identify whether exposures to ambient particles act on autonomic function via the lipid/endothelial metabolism pathway, whether effects of particulate matter <2.5 mum in aerodynamic diameter (PM(2.5)) on heart rate variability (HRV) were modified by gene polymorphisms related to those pathways were evaluated.<h4>Methods</h4>HRV a ...[more]

PMID: 19602472

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Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression

Dataset Information

Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability--the VA Normative Aging Study.

Publications

Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability--the VA Normative Aging Study.

Similar Datasets

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