Antioxidant Intervention Attenuates Myocardial Neovascularization in Hypercholesterolemia

Xiang Yang Zhu, Martin Rodriguez-Porcel, Michael D. Bentley, Alejandro R. Chade, Vincenzo Sica, Claudio Napoli, Noel Caplice, Erik L. Ritman, Amir Lerman, Lilach O. Lerman

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


Background-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)-1α and vascular endothelial growth factor (VEGF). Methods and Results-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-1α, 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/cm 2, P<0.05), which was normalized in HC+antioxidant (92.5±20.5 vessels/cm2, P<0.05 versus HC), as was arteriolar tortuosity. In addition, HC induced upregulation of VEGF, HIF-1α, and nitrotyrosine expression and decreased SOD expression and activity, all of which were preserved by antioxidant intervention. Conclusions-Changes in myocardial microvascular architecture invoked by HC are accompanied by increases in HIF-1α and VEGF expression and attenuated by antioxidant intervention. This underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early atherogenesis.

Original languageEnglish (US)
Pages (from-to)2109-2115
Number of pages7
Issue number17
StatePublished - May 4 2004


  • Antioxidant
  • Atherosclerosis
  • Hypercholesterolemia
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Antioxidant Intervention Attenuates Myocardial Neovascularization in Hypercholesterolemia'. Together they form a unique fingerprint.

Cite this