| Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1-mediated pathways. | |
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MedLine Citation:
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PMID: 19150882 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Mechanisms of air pollution-induced exacerbation of cardiovascular disease are currently unknown, thus we examined the roles of vascular endothelin-1 (ET-1) and reactive oxygen species (ROS) in regulating mediators of vascular remodeling, namely matrix metalloproteinases (MMPs), after exposure to vehicle engine emissions. METHODS AND RESULTS: ApoE(-/-) mice were exposed by inhalation to filtered air or gasoline engine exhaust (GEE, 1:12 dilution) 6 hours per day for 1 or 7 days. Concurrently, mice were treated with either ET(A) receptor antagonist BQ-123 (100 ng/kg/d) via osmotic minipumps, Tempol (approximately 41 mg/kg/d, orally), or vehicle. GEE-exposure increased vascular MMP-2 and -9, endothelin-1 (ET-1), tissue inhibitor of metalloproteinases (TIMP)-2 mRNA and ROS levels. Aortic MMP protein and plasma MMP-9 were similarly upregulated. GEE-mediated increases in vascular ROS were attenuated by Tempol-treatment, as were MMP-2 and TIMP-2; whereas BQ-123 ameliorated GEE-induced vascular expression of MMP-9, MMP-2, ROS, and ET-1. In a parallel study, diesel exhaust exposure in volunteer human subjects induced significant increases in plasma ET-1 and MMP-9 expression and activity. CONCLUSIONS: These findings demonstrate that acute exposure to vehicular source air pollutants results in upregulation of circulating and vascular factors associated with progression of atherosclerosis, mediated in part through activation of ET-1-ET(A) receptor pathways. |
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Authors:
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Amie K Lund; JoAnn Lucero; Selitá Lucas; Michael C Madden; Jacob D McDonald; Jean-Clare Seagrave; Travis L Knuckles; Matthew J Campen |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2009-01-15 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 29 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-20 Completed Date: 2009-04-02 Revised Date: 2012-06-08 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 511-7 Citation Subset: IM |
Affiliation:
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Lovelace Respiratory Research Institute,Department of Toxicology, Albuquerque, NM 87108, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Adolescent Adult Animals Antioxidants / administration & dosage Aorta / drug effects*, enzymology Apolipoproteins E / deficiency, genetics Atherosclerosis / chemically induced*, enzymology, genetics Cyclic N-Oxides / administration & dosage Endothelin-1 / blood, genetics, metabolism* Female Humans Infusion Pumps, Implantable Inhalation Exposure Male Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / blood, genetics, metabolism* Mice Mice, Knockout Nitrates / metabolism Nitrites / metabolism Peptides, Cyclic / administration & dosage RNA, Messenger / metabolism Reactive Oxygen Species / metabolism Receptor, Endothelin A / drug effects, metabolism Spin Labels Time Factors Tissue Inhibitor of Metalloproteinase-2 / metabolism Up-Regulation Vehicle Emissions / toxicity* Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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ES014639/ES/NIEHS NIH HHS; F32ES015404/ES/NIEHS NIH HHS; R01 ES014639/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Apolipoproteins E; 0/Cyclic N-Oxides; 0/Endothelin-1; 0/Nitrates; 0/Nitrites; 0/Peptides, Cyclic; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Receptor, Endothelin A; 0/Spin Labels; 0/Vehicle Emissions; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 2226-96-2/tempol; EC 3.4.24.-/Mmp9 protein, mouse; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.24/Mmp2 protein, mouse; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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