| Gene transfer of COX-1 improves lumen size and blood flow in carotid bypass grafts. | |
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MedLine Citation:
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PMID: 19361808 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: In autologous saphenous vein grafts, prostacyclin (PGI(1)), a vasoprotective molecule produced by normal endothelial cells, is down-regulated compared with ungrafted saphenous veins and normal carotid arteries. Reduced PGI(2) synthesis may contribute to local platelet deposition, vascular smooth muscle cell (VSMC) accumulation, atherosclerosis, and ultimately failure of venous bypass grafts. We have examined whether gene transfer-mediated overexpression of COX-1 in grafted veins (1) increases PGI(2) and cyclic AMP (cAMP) production, (2) leads to vasodilation and improved local blood flow in the presence of hypercholesterolemia, and (3) reduces neointima formation. MATERIALS AND METHODS: Jugular veins from New Zealand-White rabbits were incubated for 30 min ex vivo with 1 x 10(10) PFU/mL of an adenoviral vector encoding COX-1 (AdCOX-1; n = 10) or empty control (n = 10) and grafted to the carotid arteries. The rabbits were placed on a high-cholesterol diet for 4 w, and blood flow and histomorphometry of the grafts were assessed. RESULTS: In the AdCOX-1 group, blood flow was significantly increased (16.0 +/- 3.3 versus 12.5 +/- 3.3 mL/min; P < 0.05) compared with controls, and luminal area (8.9 +/- 1.4 versus 5.3 +/- 1.2 mm(2); P < 0.01) and outer circumference were larger. In six identically treated rabbits, graft PGI(2) and cAMP synthesis was increased at 72 h in AdCOX-1 compared with controls. CONCLUSION: Our data suggest a 30-min ex vivo exposure of vein grafts to AdCOX-1 increased local synthesis of PGI(2) and cAMP after graft surgery and resulted in better graft lumen and blood flow at 4 w. |
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Authors:
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Harald C Eichstaedt; Qi Liu; Zhiqiang Chen; George C Bobustuc; Toya Terry; James T Willerson; Pierre Zoldhelyi |
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Publication Detail:
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Type: Journal Article Date: 2009-01-03 |
Journal Detail:
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Title: The Journal of surgical research Volume: 161 ISSN: 1095-8673 ISO Abbreviation: J. Surg. Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-03 Completed Date: 2010-05-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376340 Medline TA: J Surg Res Country: United States |
Other Details:
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Languages: eng Pagination: 162-7 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Wafic Said Molecular Cardiology and Gene Therapy Research Laboratory, Texas Heart Institute at St Luke's Episcopal Hospital, Houston, Texas, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cholesterol / blood Cyclic AMP / biosynthesis* Cyclooxygenase 1 / genetics*, metabolism Epoprostenol / biosynthesis* Gene Therapy* Hypercholesterolemia / physiopathology Jugular Veins / metabolism, physiopathology, transplantation* Rabbits Regional Blood Flow Vasodilation* |
| Chemical | |
Reg. No./Substance:
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35121-78-9/Epoprostenol; 57-88-5/Cholesterol; 60-92-4/Cyclic AMP; EC 1.14.99.1/Cyclooxygenase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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