Document Detail

Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1-mediated pathways.
MedLine Citation:
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
Publication Detail:
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:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  29     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2009 Apr 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  511-7     Citation Subset:  IM    
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MeSH Terms
Administration, Oral
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
Inhalation Exposure
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / blood,  genetics,  metabolism*
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
Vehicle Emissions / toxicity*
Young Adult
Grant Support
Reg. No./Substance:
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 Metalloproteinase 2; EC protein, mouse; EC Metalloproteinase 9

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