MMP-9-dependent serum-borne bioactivity caused by multiwalled carbon nanotube exposure induces vascular dysfunction via the CD36 scavenger receptor

Details

• Personal Author:
  Aragon M ; Bishop L ; Campen MJ ; Erdely A ; Eye T ; Hall P ; Kodali V ; Liu J ; Ottens AK ; Salmen R ; Stafflinger JE ; Weaver J ; Zeidler-Erdely P
• Description:
  Inhalation of multi-walled carbon nanotubes (MWCNT) causes systemic effects including vascular inflammation, endothelial dysfunction, and acute phase protein expression. MWCNTs translocate only minimally beyond the lungs, thus cardiovascular effects thereof may be caused by generation of secondary biomolecular factors from MWCNT-pulmonary interactions that spill over into the systemic circulation. Therefore, we hypothesized that induced matrix metalloproteinase-9 (MMP-9) is a generator of factors that, in turn, drive vascular effects through ligand-receptor interactions with the multiligand pattern recognition receptor, CD36. To test this, wildtype (WT; C57BL/6) and MMP-9-/- mice were exposed to varying doses (10 or 40 microg) of MWCNTs via oropharyngeal aspiration and serum was collected at 4 and 24 h post-exposure. Endothelial cells treated with serum from MWCNT-exposed WT mice exhibited significantly reduced nitric oxide (NO) generation, as measured by electron paramagnetic resonance, an effect that was independent of NO scavenging. Serum from MWCNT-exposed WT mice inhibited acetylcholine-mediated relaxation of aortic rings at both time points. Absence of CD36 on the aortic rings (obtained from CD36-deficient mice) abolished the serum-induced impairment of vasorelaxation. MWCNT exposure induced MMP-9 protein levels in both bronchoalveolar lavage and whole lung lysates. Serum from MMP-9-/- mice exposed to MWCNT did not diminish the magnitude of vasorelaxation in naive WT aortic rings, although a modest right shift of the acetylcholine dose-response curve was observed in both MWCNT dose groups relative to controls. In conclusion, pulmonary exposure to MWCNT leads to elevated MMP-9 levels and MMP-9-dependent generation of circulating bioactive factors that promote endothelial dysfunction and decreased NO bioavailability via interaction with vascular CD36. [Description provided by NIOSH]
• Subjects:
  Biomarkers Cardiovascular System Cholinesterase Inhibitors Environmental Monitoring Inhalation Exposure Laboratories Lung Nitrogen Oxides Occupational Health Respiratory System Safety

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• Keywords:
  Acetylcholinesterase Author Keywords: Carbon Nanoparticle Bioactivation Blood-serum Carbon-compounds Cardiovascular Cardiovascular-function Cardiovascular-system CD36 Cell-function Cholinesterase-inhibitors Dose-response Exposure-assessment Exposure-levels Inhalants Laboratory-animals Laboratory-techniques Laboratory-testing Metalloproteins MMP-9 Nanotechnology Nitrogen-oxides Oropharynx Proteins Pulmonary-function Pulmonary-system Serum Toxicity Vascular Vasoactive-agents

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New Mexico ; OSHA Region 3 ; OSHA Region 6 ; Virginia ; 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:
  488-498
• Volume:
  150
• Issue:
  2
• NIOSHTIC Number:
  nn:20047443
• Citation:
  Toxicol Sci 2016 Apr; 150(2):488-498
• Contact Point Address:
  Matthew J. Campen, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM 87131
• Email:
  mcampen@unm.edu
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center, Albuquerque, New Mexico
• Peer Reviewed:
  True
• Start Date:
  20130901
• Source Full Name:
  Toxicological Sciences
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:44d94cf83233fed4a107f797f6cf77f4ef64df60c38d53e92ea63c79f8eff1554bf5390b8f85cfc4e7e4229ad9fd8a113143310ab28c55bb29c0d27102fa8c85
• Download URL:
  https://stacks.cdc.gov/view/cdc/202503/cdc_202503_DS1.pdf
• File Type:
  [PDF - 887.34 KB ]