| Sustained retention of tetradecylthioacetic acid after local delivery reduces angioplasty-induced coronary stenosis in the minipig. | |
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MedLine Citation:
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PMID: 11684079 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The sulfur containing tetradecylthioacetic acid (TTA) has a profound effect on lipid metabolism and may also exert antioxidant and anti-inflammatory actions and thereby counteract coronary stenosis after angioplasty balloon injury. This study examined the possible modulatory effects of TTA, delivered locally, on coronary stenosis in minipigs and the underlying mechanisms of action. METHODS: Coronary balloon angioplasty injury using an oversized balloon was performed to 40 coronary arteries (20 minipigs, Sus Scrofa, Gammelsroed) followed by delivery of placebo or TTA via a local drug delivery balloon catheter. TTA was radiolabelled in four pigs. Quantitative coronary angiography and intracoronary ultrasound (ICUS) were performed before and after injury, and after 4 weeks of follow-up. The arteries were examined with histomorphometry. The antioxidant and anti-inflammatory effects of TTA were examined on LDL oxidation and stimulated release of interleukin (IL)-2 and IL-10 in human peripheral blood mononuclear cells (PBMC), respectively. RESULTS: Radioactive TTA was present in the coronary wall after 4 weeks. Angiographic minimal luminal diameter (mean+/-S.E.M.) in the placebo and TTA group was 1.3+/-0.1 vs. 2.2+/-0.2 mm (P<0.01) at follow-up, stenosis rate was 55 and 20% (P<0.01). Remodeling was -0.56+/-0.12 in the TTA group and -1.28+/-0.09 in the placebo group (P<0.01). TTA significantly prolonged the lag time of LDL oxidation. In phytohemagglutinin stimulated PBMC, TTA significantly decreased IL-2 levels and increased IL-10 levels suggesting a marked anti-inflammatory net effect. CONCLUSIONS: Local delivery of TTA reduces coronary artery stenosis after PTCA as assessed by both angiographic, histomorphometric and ICUS examinations by influencing vessel remodeling rather than intimal hyperplasia. The underlying mechanism(s) seem to involve antioxidant and anti-inflammatory effects of this fatty acid analogue. |
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Authors:
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R J Pettersen; Z A Muna; K K Kuiper; E Svendsen; F Müller; P Aukrust; R K Berge; J E Nordrehaug |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cardiovascular research Volume: 52 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2001 Nov |
Date Detail:
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Created Date: 2001-10-30 Completed Date: 2002-01-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 306-13 Citation Subset: IM |
Affiliation:
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Department of Heart Disease, Haukeland University Hospital, N-5021, Bergen, Norway. rpet@haukland.no |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Topical Angioplasty, Transluminal, Percutaneous Coronary / adverse effects* Animals Anti-Inflammatory Agents / administration & dosage*, metabolism, pharmacology Antioxidants / administration & dosage*, metabolism, pharmacology Cells, Cultured Copper Coronary Angiography Coronary Stenosis / etiology, metabolism, prevention & control* Coronary Vessels / injuries*, metabolism, ultrasonography Female Humans Interleukin-10 / analysis Interleukin-2 / analysis Leukocytes, Mononuclear / drug effects, immunology Lipoproteins, LDL / metabolism Male Models, Animal Oxidation-Reduction Sulfides / administration & dosage*, metabolism, pharmacology Swine, Miniature Ultrasonography, Interventional |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Antioxidants; 0/Interleukin-2; 0/Lipoproteins, LDL; 0/Sulfides; 130068-27-8/Interleukin-10; 2921-20-2/1-(carboxymethylthio)tetradecane; 7440-50-8/Copper |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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