| Anti-angiogenic effect of high-dose resveratrol in a swine model of metabolic syndrome. | |
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MedLine Citation:
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PMID: 20570307 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Resveratrol has been reported to induce angiogenesis in ischemic tissue. We hypothesized that high-dose resveratrol would improve native angiogenesis in a swine model of metabolic syndrome and chronic myocardial ischemia. METHODS: Yorkshire swine were fed a normal diet (Control, n = 7), hypercholesterolemic diet (HCD, n = 7), or hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCD-R; n = 7) beginning 1 month prior to surgery. Chronic ischemia was created by placing an ameroid constrictor on the left circumflex coronary artery. After 7 weeks, swine underwent functional MRI, coronary angiography, and serum and heart tissue harvest for analysis. RESULTS: HCD-R animals had lower body mass index (P < .001), total cholesterol (P < .001), low-density lipoprotein (LDL; P < .001), blood glucose levels (P < .001), and systolic blood pressure (P = .03) than HCD animals. There was no difference in regional myocardial function at 7 weeks (P = .25). Coronary angiograms revealed no difference in Rentrop collateral scores (P = .68). Staining for platelet endothelial cell adhesion molecule-1 demonstrated higher capillary density in the Control group (versus HCD and HCD-R; P = .02). Immunoblotting demonstrated decreased expression of the pro-angiogenic protein vascular endothelial (VE)-cadherin (P = .002) and an increase in anti-angiogenic proteins angiostatin (P = .001) and thrombospondin (P = .02) in the HCD and HCD-R groups. Matrix metalloprotease 2 (MMP 2; P = .47) and MMP 9 (P = .12) were not different among groups. CONCLUSION: Supplemental resveratrol positively modified cardiovascular risk factors including body mass index, cholesterol, glucose tolerance, and systolic blood pressure. However, it did not increase native collateral formation in the ischemic myocardium. This may be a result of increased angiostatin and thrombospondin leading to decreased expression of VE-cadherin and other pro-angiogenic factors. |
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Authors:
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Michael P Robich; Louis M Chu; Mirnal Chaudray; Reza Nezafat; Yuchi Han; Richard T Clements; Roger J Laham; Warren J Manning; Michael A Coady; Frank W Sellke |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-08 |
Journal Detail:
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Title: Surgery Volume: 148 ISSN: 1532-7361 ISO Abbreviation: Surgery Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-16 Completed Date: 2010-08-06 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 0417347 Medline TA: Surgery Country: United States |
Other Details:
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Languages: eng Pagination: 453-62 Citation Subset: AIM; IM |
Copyright Information:
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Copyright 2010 Mosby, Inc. All rights reserved. |
Affiliation:
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Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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administration & dosage Angiostatins / metabolism Animals Antigens, CD / metabolism Cadherins / metabolism Cholesterol, Dietary / administration & dosage Collateral Circulation / drug effects Coronary Angiography Disease Models, Animal Magnetic Resonance Imaging Male Metabolic Syndrome X / drug therapy*, metabolism, pathology Myocardial Ischemia / drug therapy, metabolism, pathology Neovascularization, Physiologic / drug effects* Stilbenes / administration & dosage* Swine Swine, Miniature |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL046716-18A1/HL/NHLBI NIH HHS; R01 HL069024-08/HL/NHLBI NIH HHS; R01 HL069024-09/HL/NHLBI NIH HHS; R01 HL085647-03/HL/NHLBI NIH HHS; R01HL46716/HL/NHLBI NIH HHS; R01HL69024/HL/NHLBI NIH HHS; R01HL85647/HL/NHLBI NIH HHS; T32 HL076130-05/HL/NHLBI NIH HHS; T32-HL0074/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Antigens, CD; 0/Cadherins; 0/Cholesterol, Dietary; 0/Stilbenes; 0/cadherin 5; 501-36-0/resveratrol; 86090-08-6/Angiostatins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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