Document Detail


Omega-3E treatment regulates matrix metalloproteinases and prevents vascular reactivity alterations in diabetic rat aorta.
MedLine Citation:
PMID:  20029543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is known that increased generation of oxidants and (or) reduced endogenous antioxidant defense mechanisms are associated with the etiology of diabetic vascular complications. Although a close correlation exists between increased oxidative stress and the activation of matrix metalloproteinases (MMPs), little is known about the effect of hyperglycemia on the regulation and contribution of MMPs in the vascular system. Therefore, we aimed to examine whether omega-3E (50 mg/kg per day for 4 weeks), a long-chain (n-3) polyunsaturated fatty acid enriched with vitamin E, has a beneficial effect on vascular dysfunction via affecting MMPs in streptozotocin-diabetic rat aorta. Omega-3E treatment improved the diabetes-induced impairment of phenylephrine-induced contraction and isoproterenol-induced relaxation responses of aorta. It also exhibited marked protection against diabetes-induced degenerative changes in smooth muscle cell morphology. Biochemical data showed that this treatment significantly prevented important changes, such as inhibition of MMP-2 and MMP-9 activity, loss of tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) protein, increase in tissue levels of thiol oxidation, endothelin-1, protein kinase C (PKC), and cAMP production, and decrease in tissue level of nitrite. These results indicated that omega-3E significantly improved impaired vascular responses and regulated the activity of MMPs via preventing oxidative injury. Overall, the data suggest that omega-3E ameliorates or prevents vascular reactivity alterations in diabetes. Such an observation provides preliminary evidence for omega-3E's potential as a therapeutic agent for the prevention of vascular disorders in diabetes.
Authors:
Esma N Zeydanli; Belma Turan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  87     ISSN:  1205-7541     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-23     Completed Date:  2010-03-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  1063-73     Citation Subset:  IM    
Affiliation:
Department of Biophysics, Faculty of Medicine, Ankara University, Ankara 06100, Turkey.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / chemistry,  drug effects,  physiopathology*
Blotting, Western
Cyclic AMP / analysis
Diabetes Mellitus, Experimental / drug therapy,  physiopathology*
Diabetic Angiopathies / drug therapy,  physiopathology*,  prevention & control
Fatty Acids, Omega-3 / pharmacology*
Male
Matrix Metalloproteinase 2 / drug effects*,  metabolism,  physiology
Matrix Metalloproteinase 9 / drug effects*,  metabolism,  physiology
Muscle, Smooth, Vascular / drug effects,  physiopathology
Nitrites / analysis
Rats
Rats, Wistar
Vitamin E / pharmacology*
Chemical
Reg. No./Substance:
0/Fatty Acids, Omega-3; 0/Nitrites; 1406-18-4/Vitamin E; 60-92-4/Cyclic AMP; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9

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