Antioxidant intervention attenuates myocardial neovascularization in hypercholesterolemia

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-05, Vol.109 (17), p.2109-2115
• Main Authors: ZHU, Xiang-Yang, RODRIGUEZ-PORCEL, Martin, BENTLEY, Michael D, CHADE, Alejandro R, SICA, Vincenzo, NAPOLI, Claudio, CAPLICE, Noel, RITMAN, Erik L, LERMAN, Amir, LERMAN, Lilach O
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Arteriosclerosis - etiology; Ascorbic Acid - administration & dosage; Ascorbic Acid - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - therapeutic use; Coronary Circulation - drug effects; Diet, Atherogenic; Dinoprost - blood; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Enzyme Induction - drug effects; Female; Gene Expression Profiling; Gene Expression Regulation - drug effects; Heart - diagnostic imaging; Hypercholesterolemia - complications; Hypercholesterolemia - drug therapy; Hypoxia-Inducible Factor 1, alpha Subunit; Imaging, Three-Dimensional; Medical sciences; Myocardial Ischemia - etiology; Myocardial Ischemia - physiopathology; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - prevention & control; Oxidative Stress - drug effects; Superoxide Dismutase - biosynthesis; Superoxide Dismutase - genetics; Swine; Tomography, X-Ray Computed; Transcription Factors - biosynthesis; Transcription Factors - genetics; Tyrosine - analogs & derivatives; Tyrosine - biosynthesis; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vitamin E - administration & dosage; Vitamin E - therapeutic use
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000125742.65841.8B

Hypercholesterolemia (HC) and atherosclerosis can elicit oxidative stress, coronary endothelial dysfunction, and myocardial ischemia, which may induce growth-factor expression and lead to myocardial neovascularization. We tested the hypothesis that chronic antioxidant intervention in HC would attenuate neovascularization and preserve the expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF). Three groups of pigs (n=6 each) were studied after 12 weeks of normal or 2% HC diet or HC+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily). Myocardial samples were scanned ex vivo with a novel 3D micro-CT scanner, and the spatial density and tortuosity of myocardial microvessels were determined in situ. VEGF mRNA, protein levels of VEGF and VEGF receptor-1, HIF-1alpha, nitrotyrosine, and superoxide dismutase (SOD) were determined in myocardial tissue. The HC and HC+antioxidant groups had similar increases in serum cholesterol levels. HC animals showed an increase in subendocardial spatial density of microvessels compared with normal (160.5+/-11.8 versus 95.3+/-8.2 vessels/cm2, P