Lung inflammation and cardiovascular outcomes - whole blood gene expression studies in a lipopolysaccharide (LPS) pharyngeal aspiration mouse model.
Erdely-A; Salmen-R; Chapman-R; Hulderman-T; Simeonova-PP
Toxicologist 2007 Mar; 96(1):68
Recent animal and epidemiological studies suggest that pulmonary inflammation (e.g. ultrafine particulates) can trigger negative cardiovascular outcomes although the mechanism(s) resulting in systemic effects are not well established. Expression profiling of blood samples is becoming a useful tool for disease screening and identification of new biomarkers. In this study, it was hypothesized that lung inflammation results in activation of systemic gene expression related to cardiovascular disease. Prior to analyzing models of occupational exposure, pharyngeal aspiration of LPS was characterized with intraperitoneal (IP) injection as a positive control. C57BL/6 mice were treated with LPS (0.1mg/kg) and sacrificed 2hr post exposure. Whole blood and tissues were harvested for analysis of mRNA transcripts related to inflammation and coagulation. Expectedly, IP LPS resulted in a marked inflammatory response in the blood, heart and lung and pharyngeal aspiration of LPS resulted in a significant lung inflammation. Interestingly, whole blood showed similar gene expression induction of macrophage-inflammatory protein-2 (MIP-2) and tumor necrosis factor alpha (TNFá) following LPS by pharyngeal aspiration or IP injection. Extrapulmonary tissues were mostly unaffected by instillation of LPS into the lung. In conjunction with inflammation, changes in tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) have been associated with increased risk of cardiovascular disease. Neither TF nor PAI-1 gene expression was elevated in blood following IP LPS although PAI-1 was strongly induced in the heart and lung. Following pharyngeal aspiration of LPS, both TF and PAI-1 were significantly increased in the lung and whole blood but not in the heart. In conclusion, lung inflammation results in activation of inflammatory and coagulation biomarkers associated with cardiovascular diseases and blood gene expression studies can identify biomarkers which predict cardiovascular outcomes in occupational-related respiratory exposures.
Cell-alteration; Cell-damage; Cellular-reactions; Cell-biology; Cell-function; Cell-metabolism; Cell-morphology; Cell-transformation; Epidemiology; Pulmonary-disorders; Pulmonary-system-disorders; Lung-disorders; Biomarkers; Blood-samples; Blood-analysis; Blood-cells; Tissue-disorders; Animal-studies; Genetic-disorders; Laboratory-animals; Nanotechnology
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina