|Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1-mediated pathways.|
|PMID: 19150882 Owner: NLM Status: MEDLINE|
|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.
|Amie K Lund; JoAnn Lucero; Selitá Lucas; Michael C Madden; Jacob D McDonald; Jean-Clare Seagrave; Travis L Knuckles; Matthew J Campen|
|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2009-01-15|
|Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 29 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2009 Apr|
|Created Date: 2009-03-20 Completed Date: 2009-04-02 Revised Date: 2014-09-01|
Medline Journal Info:
|Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States|
|Languages: eng Pagination: 511-7 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
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*
Infusion Pumps, Implantable
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / blood, genetics, metabolism*
Nitrates / metabolism
Nitrites / metabolism
Peptides, Cyclic / administration & dosage
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism
Receptor, Endothelin A / drug effects, metabolism
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Vehicle Emissions / toxicity*
|ES014639/ES/NIEHS NIH HHS; F32ES015404/ES/NIEHS NIH HHS; R01 ES014639/ES/NIEHS NIH HHS|
|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 184.108.40.206/Matrix Metalloproteinase 2; EC 220.127.116.11/Mmp2 protein, mouse; EC 18.104.22.168/Matrix Metalloproteinase 9|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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