Document Detail

Evidence for 12-lipoxygenase induction in the vessel wall following balloon injury.
MedLine Citation:
PMID:  10341849     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Vascular smooth muscle cell (VSMC) migration and proliferation are key events in the development of atherosclerosis and restenosis following angioplasty. These events are mediated by several growth factors and cytokines whose cellular effects include activation of phospholipases and arachidonic acid metabolism via the lipoxygenase (LO) pathway. Since 12-LO products have potent growth and chemotactic effects, we have examined if 12-LO is upregulated in the neointima of injured rat carotid arteries and also if LO inhibition could attenuate neointimal thickening. METHODS: The left common carotid arteries of male Sprague Dawley rats were injured using a 1.8 F PTCA balloon catheter. Four-fourteen days after injury, injured and uninjured tissue samples were processed for histology, and immunohistochemistry or polymerase chain reaction (PCR) to examine 12-LO expression. RESULTS: Twelve days after injury, immunohistochemical staining with a 12-LO antibody revealed intense staining in injured left carotid arteries, mainly in neointimal VSMCs and inflammatory cells, but not in the uninjured right arteries. There was also a marked upregulation of 12-LO mRNA (over five-fold by competitive PCR) in the injured arteries. Treatment of the arteries with a LO inhibitor, phenidone, soon after injury resulted in significant inhibition of neointimal thickening. In contrast, a cyclooxygenase inhibitor, ibuprofen, had no effect. CONCLUSIONS: These results indicate for the first time that balloon injury results in marked induction of 12-LO mRNA and protein expression in the vessel wall. Furthermore, LO pathway activation may mediate, at least in part, the development of the lesion or plaque instability, suggesting a novel target for therapeutic intervention to block these pathological events.
R Natarajan; H Pei; J L Gu; J M Sarma; J Nadler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cardiovascular research     Volume:  41     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-06-07     Completed Date:  1999-06-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  489-99     Citation Subset:  IM    
Department of Diabetes, Endocrinology and Metabolism, Gonda Diabetes Center, City of Hope Medical Center, Duarte, CA 91010, USA.
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MeSH Terms
Analysis of Variance
Angioplasty, Balloon / adverse effects*
Arachidonate 12-Lipoxygenase / genetics,  metabolism*
Carotid Artery, Common
Enzyme Induction / drug effects
Gene Expression
Lipoxygenase Inhibitors / pharmacology
Muscle, Smooth, Vascular / drug effects,  enzymology,  injuries*
Neovascularization, Pathologic
Polymerase Chain Reaction
Pyrazoles / pharmacology
Rats, Sprague-Dawley
Tunica Intima / enzymology*
Grant Support
Reg. No./Substance:
0/Lipoxygenase Inhibitors; 0/Pyrazoles; 92-43-3/phenidone; EC 12-Lipoxygenase

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