World Trade Center-Cardiorespiratory and Vascular Dysfunction: Assessing the Phenotype and Metabolome of a Murine Particulate Matter Exposure Model

Details

• Personal Author:
  Crowley G ; Gironda Z ; Kwon S ; Liu M ; Mikhail M ; Nolan A ; Oskuei A ; Ostrofsky D ; Vaidyanathan S ; Veerappan A ; Wadghiri YZ
• Description:
  Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World Trade Center-Particulate Matter (WTC-PM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of WTC-PM53 or phosphate-buffered saline (PBS) (controls). 24-hours (24-hrs) and 1-Month (1-M) after exposure, echocardiography, micro-positron emission tomography(µ-PET), collagen quantification, lung metabolomics, assessment of antioxidant potential and soluble-receptor for advanced glycation end products (sRAGE) in bronchoalveolar lavage(BAL) and plasma were performed. 24-hrs post-exposure, there was a significant reduction in (1) Pulmonary artery(PA) flow-velocity and pulmonary ejection time(PET) (2) Pulmonary acceleration time(PAT) and PAT/PET, while (3) Aortic ejection time(AET) and velocity time integral(VTI) were increased, and (4) Aortic acceleration time (AAT)/AET, cardiac output and stroke volume were decreased compared to controls. 1-M post-exposure, there was also significant reduction of right ventricular diameter as right ventricle free wall thickness was increased and an increase in tricuspid E, A peaks and an elevated E/A. The pulmonary and cardiac standard uptake value and volume 1-M post-exposure was significantly elevated after PM-exposure. Similarly, ?-smooth muscle actin(?-SMA) expression, aortic collagen deposition was elevated 1-M after PM exposure. In assessment of the metabolome, prominent subpathways included advanced glycation end products (AGEs), phosphatidylcholines, sphingolipids, saturated/unsaturated fatty acids, eicosanoids, and phospholipids. BAL superoxide dismutase(SOD), plasma total-antioxidant capacity activity, and sRAGE (BAL and plasma) were elevated after 24-hrs. PM exposure and associated vascular disease are a global health burden. Our study shows persistent WTC-Cardiorespiratory and Vascular Dysfunction (WTC-CaRVD), inflammatory changes and attenuation of antioxidant potential after PM exposure. Early detection of vascular disease is crucial to preventing cardiovascular deaths and future work will focus on further identification of bioactive therapeutic targets. [Description provided by NIOSH]
• Subjects:
  Biomarkers Blood Cardiovascular Diseases Cardiovascular System Energy Metabolism Environmental Exposure Histology Immune System Laboratories Lung Occupational Health Particulate Matter Respiratory System Safety September 11 Terrorist Attacks

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• Keywords:
  Airway Obstruction Analytical Models Blood Vessels Cardiac Function Cardiopulmonary Function Cardiopulmonary System Disorders Cardiovascular Disease Cardiovascular Function Cardiovascular System Disease Environmental Exposure Exposure Assessment Exposure Levels Health Effects Heart Humans Immunochemistry Laboratory Animals Laboratory Testing Metabolism Oxidative Stress Particulates World Trade Center WTC

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• ISSN:
  2045-2322
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  10
• NIOSHTIC Number:
  nn:20058708
• Citation:
  Sci Rep 2020 Feb; 10:3130
• Contact Point Address:
  Anna Nolan, Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, NYU, School of Medicine, New York, NY, USA
• Email:
  anna.nolan@med.nyu.edu
• Federal Fiscal Year:
  2020
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  Scientific Reports
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:724782d22600110b6796f2fd0cb1c0645ce8a974bd31e911e4036aa37fe69f13e80df49efa674fc85fd76626c2d576b334d8c8edcd4c629e62a1cb332c89a9d7
• Download URL:
  https://stacks.cdc.gov/view/cdc/223109/cdc_223109_DS1.pdf
• File Type:
  [PDF - 2.97 MB ]