Thrombospondin-1 mediates multi-walled carbon nanotube-induced impairment of arteriolar dilation

Details

• Personal Author:
  Mandler WK ; Nurkiewicz TR ; Olfert IM ; Porter DW
• Description:
  Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) and other nanomaterials has been shown to disrupt endothelium-dependent arteriolar dilation in the peripheral microcirculation. The molecular mechanisms behind these arteriolar disruptions have yet to be fully elucidated. The secreted matricellular matrix protein thrombospondin-1 (TSP-1) is capable of moderating arteriolar vasodilation by inhibiting soluble guanylate cyclase activity. We hypothesized that TSP-1 may be a link between nanomaterial exposure and observed peripheral microvascular dysfunction. To test this hypothesis, wild-type C57B6J (WT) and TSP-1 knockout (KO) mice were exposed via lung aspiration to MWCNT or a sham dispersion medium control. Following exposure (24hrs), arteriolar characteristics and reactivity were measured in the gluteus maximus muscle using intravital microscopy (IVM) coupled with microiontophoretic delivery of acetylcholine (ACh) or sodium nitroprusside (SNP). In WT mice exposed to MWCNT, skeletal muscle TSP-1 protein increased > 5-fold compared to sham exposed, and exhibited a 39% and 47% decrease in endothelium-dependent and independent vasodilation, respectively. In contrast, TSP-1 protein was not increased following MWCNT exposure in KO mice and exhibited no loss in dilatory capacity. Microvascular leukocyte activation was measured by assessing third order venular leukocyte adhesion and rolling activity. The WT + MWCNT group demonstrated 223% higher leukocyte rolling compared to WT + SHAM controls. TSP-1 KO animals exposed to MWCNT showed no differences from WT + SHAM control. These data provide evidence that TSP-1 mediates, in part, the systemic microvascular dysfunction in the periphery that follows pulmonary ENM exposure. [Description provided by NIOSH]
• Subjects:
  Blood Cardiovascular Diseases Cardiovascular System Laboratories Lung Microbiology Musculoskeletal System Occupational Health Respiratory System Safety Toxicology

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• Keywords:
  Blood Vessels Carbon Nanotubes Cardiovascular Function Cardiovascular System Disorders Endothelial Cells Exposure Assessment Heart Laboratory Animals Laboratory Testing Leukocytes Lymphatic System Microscopic Analysis Multi-walled Carbon Nanotubes Muscle Tissue MWCNT Nanotechnology Nanotoxicology Nanotubes Proteins Pulmonary System Skeletal System Tissue Culture Vasoactive Agents Veins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049476
• Citation:
  Toxicologist 2017 Mar; 156(1):404
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:31c8773ba928655c5874f76a6f359d8e51d2e34108bed74200c99094a27accbf78f6d60f65336cba06ceddedfe6fe1094cc1d8e06a52db095ca706a399050f64
• Download URL:
  https://stacks.cdc.gov/view/cdc/203918/cdc_203918_DS1.pdf
• File Type:
  [PDF - 945.08 KB ]