Evidence for mechanistic specificity driving pulmonary particulate exposure-induced cardiovascular dysfunction

Details

• Personal Author:
  Erdely A
• Description:
  Adverse cardiovascular effects following a pulmonary particulate exposure are well documented. Exposure to incidental and engineered nanosized materials can alter vascular responsiveness and cause morphologic changes. While particle translocation and neurogenic effects are proposed, recent experimental evidence suggests an alteration in circulating mediators as the predominant mechanism. These studies demonstrate that localized pulmonary responses are often distinct from systemic toxicity. For example, vascular function was unchanged following a nanosilver exposure despite lung injury, increased inflammatory cell influx, and induction of inflammatory genes. Conversely, an incidental nanoparticle exposure to resistance spot welding particles induced marked vascular dysfunction with no alterations in general lung toxicity or inflammation. Following a 10 d ultrafine metal-rich particulate inhalation exposure, molecular signaling induced at the site of exposure was reflected systemically in the circulating leukocytes as well as cardiovascular tissues. The responses predicted cardiac mitochondrial dysfunction and compensation that were confirmed by functional studies. The systemic effects resolved following cessation of exposure despite sustained and, in some cases, increasing lung injury and inflammation one month later. Serum from mice exposed to multi-walled carbon nanotubes (MWCNT) attenuated vascular dilation, decreased nitric oxide production, and induced cellular inflammation. Unlike the pulmonary response, these effects were independent of dose. In contrast to serum of wild-type mice, maximal vascular dilation was achieved with serum collected from MWCNT-exposed MMP9-/- mice. While maximal dilation was restored, lung inflammatory markers were similar to wild-type exposed mice despite predictions that MMP9 would be a primary driver of pulmonary responses to MWCNT. These results indicate that altered circulating factors contributing to vascular dysfunction had mechanistic specificity. In summary, cardiovascular effects following a pulmonary exposure do not necessarily correlate with general measures of pulmonary toxicity and inflammation and were not always dose-dependent. In addition, specific molecular mechanisms induced by an exposure can drive cardiovascular dysfunction via altered circulating mediators. [Description provided by NIOSH]
• Subjects:
  Cardiovascular Diseases Cardiovascular System Dust Immune System Laboratories Lung Lung Diseases Metals Nitric Oxide Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Biological Effects Biological Systems Carbon Nanotubes Cardiac Function Cardiovascular System Cardiovascular System Disorders Cell Function Cellular Effects Cellular Reactions Exposure Assessment Immune Reaction Immune System Inhalation Laboratory Animals Laboratory Testing Leukocytes Lung Disorders Lung Function Metal Dusts Molecular Signaling Multi-walled Carbon Nanotubes MWCNT Nanoparticles Nanotechnology Nanotoxicology Nanotubes Nitric Oxide Pulmonary Function Pulmonary System Serological Techniques Ultrafine Particles

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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:20049445
• Citation:
  Toxicologist 2017 Mar; 156(1):320
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• 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:c31a97c04e5c3b636fcbcc9fcfa9a578ddb0bf210d9ff4ff67713d5b750ea0735442eb67940a6803a040d7b701189e054a044f7c84a101709297ab986091fabf
• Download URL:
  https://stacks.cdc.gov/view/cdc/203889/cdc_203889_DS1.pdf
• File Type:
  [PDF - 942.97 KB ]