Abstract | OBJECTIVE: The purpose of the present study was to evaluate the effect of atorvastatin on oxidative stress and angiogenesis in ischemic myocardium in a clinically relevant porcine model of the metabolic syndrome. METHODS: Sixteen Ossabaw pigs were fed either a high-fat diet alone or a high-fat diet supplemented with atorvastatin (1.5 mg/kg daily) for 14 weeks. Chronic myocardial ischemia was induced by ameroid constrictor placement around the circumflex artery. After 6 months of the diet, myocardial perfusion was measured at rest and with demand pacing. The heart was harvested for analysis of perfusion, microvessel relaxation, protein expression, and oxidative stress. RESULTS: Both groups had similar endothelium-dependent microvessel relaxation to adenosine diphosphate and endothelium-independent relaxation to sodium nitroprusside. Myocardial perfusion in the ischemic territory was also not significantly different either at rest or with demand pacing. Atorvastatin treatment increased total myocardial protein oxidation and serum lipid peroxidation. However, the expression of markers of oxidative stress, including NOX2, RAC1, myeloperoxidase, and superoxide dismutase 1, 2, and 3, were not statistically different. The expression of proangiogenic proteins endothelial nitric oxide synthase, phosphorylated endothelial nitric oxide synthase (Ser 1177), phosphorylated adenosine monophosphate kinase (Thr 172), phosphorylated extracellular signal-regulated kinase (T202, Y204), and vascular endothelial growth factor were all upregulated in the atorvastatin group. CONCLUSIONS:
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Authors | Nassrene Y Elmadhun, Antonio D Lassaletta, Louis M Chu, Yuhong Liu, Jun Feng, Frank W Sellke |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 144
Issue 6
Pg. 1486-93
(Dec 2012)
ISSN: 1097-685X [Electronic] United States |
PMID | 22995723
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Angiogenesis Inducing Agents
- Angiogenic Proteins
- Biomarkers
- Heptanoic Acids
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Pyrroles
- Vasodilator Agents
- Atorvastatin
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Topics |
- Angiogenesis Inducing Agents
(pharmacology)
- Angiogenic Proteins
(metabolism)
- Animals
- Atorvastatin
- Biomarkers
(blood)
- Collateral Circulation
(drug effects)
- Coronary Circulation
(drug effects)
- Diet, High-Fat
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Fibrosis
- Heptanoic Acids
(pharmacology)
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(pharmacology)
- Lipid Peroxidation
(drug effects)
- Male
- Metabolic Syndrome
(blood, complications, drug therapy, physiopathology)
- Microvessels
(drug effects, metabolism, physiopathology)
- Myocardial Ischemia
(blood, complications, drug therapy, physiopathology)
- Myocardial Perfusion Imaging
- Myocardium
(metabolism, pathology)
- Neovascularization, Physiologic
(drug effects)
- Oxidative Stress
(drug effects)
- Pyrroles
(pharmacology)
- Signal Transduction
(drug effects)
- Swine
- Swine, Miniature
- Vasodilation
(drug effects)
- Vasodilator Agents
(pharmacology)
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