MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor

Toxicological Sciences : an Official Journal of the Society of Toxicology
Mario AragonMatthew J Campen

Abstract

Inhalation of multiwalled 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 µg) of MWCNTs via oropharyngeal aspiration and serum was collected at 4 and 24 h postexposure. 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 (ACh)-mediated relaxation of aortic rings at both time points. Absence of CD36 on the aortic rings (obtained from CD36-deficient mice) abolishe...Continue Reading

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Citations

May 23, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·William Kyle MandlerIvan Mark Olfert
Apr 17, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Katherine E ZychowskiMatthew J Campen
Aug 2, 2017·Antioxidants & Redox Signaling·Amanda J LeBlanc, Natia Q Kelm
Nov 2, 2018·Cardiovascular Toxicology·Leslie C ThompsonChristopher J Wingard
May 31, 2019·International Journal of Molecular Sciences·Brandi N Snyder-TalkingtonNancy L Guo
Feb 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Mario J AragonMatthew J Campen
Aug 15, 2019·Cardiovascular Toxicology·Katherine E ZychowskiMatthew J Campen
May 31, 2019·Particle and Fibre Toxicology·Ekaterina MostovenkoAndrew K Ottens
Jun 10, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Vamsi KodaliAaron Erdely
Mar 9, 2021·Journal of Toxicology and Environmental Health. Part a·Alexis WilsonKatherine E Zychowski
Apr 24, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ekaterina MostovenkoAndrew K Ottens

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