Altered Functional and Molecular Responses of Endothelial Cells Treated with Serum Collected from Rats Exposed to Different Welding Fumes

Details

• Personal Author:
  Antonini JM ; Erdely A ; Eye T ; Kodali V ; Meighan TG ; Shoeb M ; Stueckle, Todd A.
• Description:
  Epidemiological studies suggest an interplay between exposure to particulate matter and the rise in adverse cardiovascular outcomes. The precise mechanism of how pulmonary exposure translates to cardiovascular dysfunction is largely unknown. Recent studies suggest alterations in circulating factors as the primary cause of pulmonary-induced cardiovascular dysfunction. Because serum is composed of a myriad of discrete biochemical components, it is not only costly but selection affects the bias measurement of individual components. Because vascular endothelial cells play a pivotal role in cardiovascular disorders, we used serum collected from exposed animals to assess its molecular and functional effects on in vitro cultures of primary cardiac microvascular endothelial (PCME) cells or ex vivo cultured aortas from naïve rats as a strategy for evaluating altered endothelial cell function. This approach was validated using serum obtained from Sprague-Dawley rats at 24 h after intratracheal instillation of 2 mg/rat of different welding fumes (WF): manual metal arc welding using stainless steel electrodes (MMASS) and gas metal arc welding using mild steel electrodes (GMA-MS) or PBS (vehicle control). As an initial screen, PCME cells from rats were challenged for 4 h with serum from WF or vehicle-exposed animals, and 84 genes related to endothelial cell biology were analyzed from the mRNA isolated from challenged cells. In order to understand the functional and biological impact of the differentially expressed genes, Ingenuity Pathway Analysis (IPA) was performed. IPA predicted that serum from animals exposed to MMA-SS, and not GMA-MS or PBS, had influence on several functional aspects of endothelial cells, including angiogenesis and migration. These functional predictions were further validated with a scratch assay for migration (in vitro) and aortic ring assay for angiogenesis (ex vivo). As predicted, both functional endpoints were significantly changed when challenged with serum from MMA-SS but not GMA-MS, suggesting that pulmonary MMA-SS exposure has the potential to cause altered endothelial function systemically. This methodology can easily be adapted to a high-throughput screening platform and be utilized as a quick primary screening strategy for evaluating systemic cardiovascular toxicity due to various pulmonary exposures. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Animals Biological Assay Blood Cardiovascular Diseases Cardiovascular System Environmental Exposure Epidemiology Hazardous Substances Laboratories Lung Metals Occupational Health Particulate Matter Respiratory System Safety Toxicology Welding

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• Keywords:
  Angiogenesis Arc Welding Bioassays Blood Plasma Blood Vessels Cardiovascular System Disorders Cell Alteration Cell Migration Cellular Function Endothelial Cells Exposure Assessment Exposure Levels Gas Welders Laboratory Animals Laboratory Testing Lymphatic System Medical Screening Particulates Pulmonary System Screening Methods Toxic Effects Toxic Fumes Welding Fumes

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  46
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051142
• Citation:
  Toxicologist 2018 Mar; 162(1):46
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:91aa73513dbd1e8b91c6255ac47fb4954d248f3e48501284463350d2c250005cf50cadd3a5886549cbf2364c7e58a420fe2d0e746717b619ebb8155b26488614
• Download URL:
  https://stacks.cdc.gov/view/cdc/211250/cdc_211250_DS1.pdf
• File Type:
  [PDF - 838.84 KB ]